Chapter 7 Flashcards
(312 cards)
1
Q
Front
A
Back
2
Q
What are skeletal muscle fibers innervated by?
A
Skeletal muscle fibers are innervated by large myelinated nerve fibers that originate from large motoneurons in the anterior horns of the spinal cord.
3
Q
How many skeletal muscle fibers can each nerve fiber stimulate?
A
Each nerve fiber after entering the muscle belly normally branches and stimulates from three to several hundred skeletal muscle fibers.
4
Q
What is the neuromuscular junction?
A
The neuromuscular junction is a junction made by each nerve ending with a muscle fiber typically located near the midpoint of the muscle fiber.
5
Q
How does the action potential travel in a muscle fiber after it is initiated by a nerve signal?
A
The action potential initiated in the muscle fiber by the nerve signal travels in both directions toward the ends of the muscle fiber.
6
Q
How many neuromuscular junctions are typically found on a muscle fiber?
A
With the exception of about 2% of muscle fibers there is only one neuromuscular junction per muscle fiber.
7
Q
What are the components of the neuromuscular junction?
A
The neuromuscular junction consists of the presynaptic terminal (nerve ending) synaptic cleft and the postsynaptic membrane (motor end plate) of the muscle fiber.
8
Q
What role does the motor end plate play in neuromuscular transmission?
A
The motor end plate is the specialized area of the muscle membrane that contains receptors for the neurotransmitter released from the nerve ending facilitating the transmission of impulses to the muscle fiber.
9
Q
What happens when the nerve signal stimulates the muscle fiber?
A
When the nerve signal stimulates the muscle fiber it results in an action potential that leads to muscle contraction.
10
Q
Describe the structure of the motor end plate.
A
The motor end plate is characterized by folds that increase the surface area for receptor sites facilitating a greater interaction with the neurotransmitter.
11
Q
What neurotransmitter is primarily involved in neuromuscular transmission?
A
Acetylcholine (ACh) is the primary neurotransmitter involved in neuromuscular transmission.
12
Q
What occurs when acetylcholine binds to receptors at the motor end plate?
A
When acetylcholine binds to its receptors at the motor end plate it causes depolarization of the muscle fiber leading to the initiation of an action potential.
13
Q
What is the impact of an action potential on muscle contraction?
A
The action potential triggers a series of events that lead to muscle contraction through excitation-contraction coupling.
14
Q
Explain the term ‘excitation-contraction coupling’.
A
Excitation-contraction coupling is the physiological process in which an action potential leads to muscle contraction involving the release of calcium ions from the sarcoplasmic reticulum.
15
Q
What role does the sarcoplasmic reticulum play in muscle contraction?
A
The sarcoplasmic reticulum stores calcium ions and releases them in response to an action potential which is critical for muscle contraction.
16
Q
What occurs at the neuromuscular junction during muscle fiber stimulation?
A
During muscle fiber stimulation acetylcholine is released from the presynaptic nerve terminal into the synaptic cleft binds to receptors on the motor end plate and initiates a depolarization that leads to an action potential.
17
Q
What can lead to paralysis at the neuromuscular junction?
A
Paralysis at the neuromuscular junction can occur due to several factors including the blockage of acetylcholine receptors or the degradation of acetylcholine. Conditions like myasthenia gravis can affect this process.
18
Q
How do myelinated nerve fibers affect the speed of signal transmission to skeletal muscle fibers?
A
Myelinated nerve fibers allow for faster signal transmission due to saltatory conduction where the action potential jumps from one node of Ranvier to the next.
19
Q
What is the significance of having multiple branches of a nerve fiber within a muscle?
A
The significance of having multiple branches of a nerve fiber within a muscle is to allow the simultaneous stimulation of numerous muscle fibers enabling coordinated muscle contractions.
20
Q
What is the motor end plate?
A
The motor end plate is a structure formed where a myelinated nerve fiber branches and invaginates into the surface of a skeletal muscle fiber lying outside the muscle fiber plasma membrane.
21
Q
What are Schwann cells and their function at the motor end plate?
A
Schwann cells are glial cells that surround the motor end plate providing insulation from surrounding fluids.
22
Q
Describe the synaptic gutter or synaptic trough.
A
The synaptic gutter also known as the synaptic trough is an invaginated membrane at the junction between the axon terminal and the muscle fiber membrane.
23
Q
What is the width of the synaptic cleft?
A
The synaptic cleft is between 20 to 30 nanometers wide.
24
Q
What are subneural clefts and their significance at the motor end plate?
A
Subneural clefts are numerous smaller folds of the muscle membrane at the bottom of the synaptic gutter that greatly increase the surface area for the action of synaptic transmitters.
25
What is the role of mitochondria in the axon terminal?
Mitochondria in the axon terminal supply adenosine triphosphate (ATP) which is the energy source used for the synthesis of neurotransmitters.
26
What is adenosine triphosphate (ATP) and its importance in synaptic transmission?
ATP is a nucleotide that serves as an energy source for cellular processes including the synthesis of neurotransmitters at the nerve terminal.
27
Explain the relationship between a myelinated nerve fiber and a skeletal muscle fiber at the motor end plate.
The myelinated nerve fiber connects to a skeletal muscle fiber at the motor end plate forming a junction where neurotransmission occurs for muscle contraction.
28
How does the structure of the motor end plate facilitate neurotransmission?
The structure of the motor end plate including the synaptic gutter synaptic cleft and subneural clefts maximizes surface area for neurotransmitter action enhancing the efficiency of neurotransmission.
29
What components are involved in the synaptic transmission process at the motor end plate?
Components involved include the nerve fiber (axon terminal) muscle fiber membrane synaptic cleft synaptic gutter neurotransmitters and ATP for energy.
30
What is acetylcholine?
Acetylcholine is a neurotransmitter that excites the muscle fiber membrane playing a crucial role in the neuromuscular junction transmission.
31
Where is acetylcholine synthesized?
Acetylcholine is synthesized in the cytoplasm of the nerve terminal.
32
How many synaptic vesicles containing acetylcholine are typically found in a single end plate terminal?
About 300000 synaptic vesicles containing acetylcholine are normally present in the terminals of a single end plate.
33
What is the function of acetylcholinesterase?
Acetylcholinesterase is an enzyme located in the synaptic space that destroys acetylcholine a few milliseconds after it has been released from the synaptic vesicles.
34
What happens when a nerve impulse reaches the neuromuscular junction?
When a nerve impulse reaches the neuromuscular junction approximately 125 vesicles of acetylcholine are released from the nerve terminals into the synaptic space.
35
Describe the synaptic space at the neuromuscular junction.
The synaptic space is the area between the neural membrane above and the muscle membrane with its subneural clefts below. It contains numerous synaptic vesicles of acetylcholine and the enzyme acetylcholinesterase.
36
What is indicated by the 'linear dense bars' on the inside surface of the neural membrane?
The linear dense bars on the inside surface of the neural membrane are structural features that play a role in the release of neurotransmitters like acetylcholine.
37
What occurs immediately after acetylcholine is released into the synaptic space?
After acetylcholine is released into the synaptic space it is quickly destroyed by the enzyme acetylcholinesterase.
38
What role do the protein particles next to the dense bars play?
The protein particles next to the dense bars are involved in the mechanisms of neurotransmitter release and may contribute to the organization and function of the synaptic structures.
39
What are voltage-gated calcium channels responsible for in a nerve terminal?
Voltage-gated calcium channels open when an action potential spreads over the nerve terminal allowing calcium ions to diffuse into the interior of the terminal from the synaptic space.
40
What role do calcium ions play in neurotransmitter release?
Calcium ions activate calmodulin-dependent protein kinase (CaMK) which phosphorylates synapsin proteins that anchor acetylcholine vesicles to the cytoskeleton of the presynaptic terminal facilitating their release.
41
What is the significance of synapsin proteins in neurotransmitter release?
Synapsin proteins anchor acetylcholine vesicles to the cytoskeleton preventing their premature release. When phosphorylated by CaMK they release the vesicles allowing them to move towards the active zone for release.
42
Describe the process following the entry of calcium ions into the nerve terminal. What happens to the acetylcholine vesicles?
After calcium ions enter the nerve terminal they activate CaMK leading to the phosphorylation of synapsin proteins. This relieves the anchoring of acetylcholine vesicles to the cytoskeleton allowing them to move to the active zone dock at release sites fuse with the neural membrane and release acetylcholine through exocytosis.
43
What is exocytosis in the context of neurotransmitter release?
Exocytosis is the process by which vesicles containing neurotransmitters such as acetylcholine fuse with the presynaptic neuron's membrane and release their contents into the synaptic space.
44
What is the effective stimulus for causing the release of acetylcholine from vesicles?
The entry of calcium ions into the nerve terminal is the effective stimulus that causes the release of acetylcholine from the vesicles.
45
How do calcium ions influence synapsin proteins?
Calcium ions activate calmodulin-dependent protein kinase (CaMK) which phosphorylates synapsin proteins leading to the release of acetylcholine vesicles from the cytoskeleton.
46
Discuss the overall sequence of events that lead to acetylcholine release at the synapse. Include key players and processes.
The sequence begins with an action potential reaching the nerve terminal opening voltage-gated calcium channels. Calcium ions diffuse into the terminal activating CaMK which phosphorylates synapsin proteins. This phosphorylation allows acetylcholine vesicles to detach from the cytoskeleton move to the active zone dock at release sites fuse with the membrane and release acetylcholine into the synaptic space via exocytosis.
47
What is the role of the active zone in neurotransmitter release?
The active zone is the site on the presynaptic membrane where vesicles dock to be released. It is adjacent to dense bars and is crucial for the fusion of vesicles and release of neurotransmitters.
48
What might be considered speculative details in the process of acetylcholine release?
Though the involvement of calcium ions in triggering acetylcholine release is well-established certain specific details about the mechanism and the roles of other proteins may be considered speculative.
49
What is acetylcholine and where is it found in the context of nerve and muscle function?
Acetylcholine is a neurotransmitter that is released from the vesicles in the nerve terminals adjacent to the dense bars of the motor end plate which is crucial for muscle contraction.
50
Describe the structure of the motor end plate based on the longitudinal section view.
The longitudinal section of the motor end plate shows distinct components including a myelinated axon terminal nerve branches muscle nuclei teloglial cells and myofibrils illustrating their spatial relationships.
51
What are the key components observed in the surface view of the motor end plate?
The surface view displays synaptic vesicles the axon terminal situated within the synaptic trough and subneural clefts highlighting the arrangement and interaction among these components.
52
What role do synaptic vesicles play at the motor end plate?
Synaptic vesicles store acetylcholine and release it into the synaptic cleft to transmit signals from the nerve to the muscle fiber initiating contraction.
53
What is the function of the dense bars in the motor end plate?
Dense bars serve as attachment sites where synaptic vesicles fuse with the membrane to release acetylcholine into the synaptic cleft.
54
Explain the significance of teloglial cells at the motor end plate.
Teloglial cells provide structural support and play a role in the maintenance of the motor end plate potentially influencing neurotransmission efficiency.
55
Describe the electron micrographic appearance of a single axon terminal contacting a muscle fiber membrane.
An electron micrograph would reveal the close contact between the axon terminal and the muscle fiber membrane indicating synaptic transmission points where neurotransmitter release occurs.
56
What is the function of subneural clefts in the motor end plate?
Subneural clefts are invaginations in the muscle fiber membrane; they increase the surface area available for acetylcholine receptors enhancing the efficiency of synaptic transmission.
57
How does the release of acetylcholine affect muscle fibers?
The binding of acetylcholine to its receptors on the muscle fiber membrane triggers depolarization and ultimately leads to muscle contraction.
58
What visual features distinguish a synaptic trough in the surface view of the motor end plate?
The synaptic trough is characterized by its depression in the muscle fiber membrane that accommodates the axon terminal facilitating effective neurotransmission.
59
What is the neuromuscular junction?
The neuromuscular junction is the synapse or connection point between a motor neuron and a muscle fiber where the motor neuron communicates with the muscle to trigger contraction.
60
Describe the role of acetylcholine in the neuromuscular junction.
Acetylcholine is a neurotransmitter released from the synaptic vesicles of the motor neuron at the neuromuscular junction. It binds to acetylcholine receptors on the muscle fiber's membrane leading to depolarization and subsequently muscle contraction.
61
What is the function of acetylcholine receptors in the muscle membrane?
Acetylcholine receptors are located in the muscle membrane at the neuromuscular junction specifically at the mouths of subneural clefts. When acetylcholine binds to these receptors it opens ion channels allowing sodium ions to flow into the muscle cell resulting in depolarization and muscle contraction.
62
What are subneural clefts?
Subneural clefts are invaginations or folds in the muscle fiber membrane located at the neuromuscular junction. These structures increase the surface area for acetylcholine receptors optimizing the neuromuscular transmission process by ensuring that released acetylcholine quickly binds to its receptors.
63
Explain the significance of the proximity of release sites to acetylcholine receptors at the neuromuscular junction.
The close proximity of the acetylcholine release sites in the neural membrane to the acetylcholine receptors in the muscle membrane ensures efficient synaptic transmission. This spatial arrangement facilitates rapid communication between the neuron and the muscle fiber crucial for timely muscle contractions.
64
What is the relationship between acetylcholine and voltage-gated sodium channels in the neuromuscular junction?
Once acetylcholine binds to its receptors on the muscle membrane it causes the opening of ion channels which leads to the depolarization of the membrane. This depolarization activates voltage-gated sodium channels allowing sodium ions to enter the muscle cell further propagating the action potential and facilitating muscular contraction.
65
What visual representation is referred to in the text and what does it illustrate?
The text refers to an electron micrographic view (Figure 7-2) that illustrates the neuromuscular junction specifically showing the release of acetylcholine from synaptic vesicles and the close arrangement of these release sites to acetylcholine receptors on the muscle fiber membrane.
66
What happens to the muscle fiber membrane when acetylcholine binds to its receptors?
When acetylcholine binds to its receptors on the muscle fiber membrane it causes the opening of ion channels leading to an influx of sodium ions resulting in depolarization of the muscle fiber membrane and triggering muscle contraction.
67
What are the acetylcholine-gated ion channels and where are they located?
Acetylcholine-gated ion channels are located almost entirely near the mouths of the subneural clefts in the muscle fiber membrane. They are crucial for signal transmission at the neuromuscular junction.
68
What is illustrated in the figure of the postsynaptic membrane?
The figure illustrates the postsynaptic membrane highlighting the presence of acetylcholine receptors and voltage-gated sodium channels near the subneural clefts.
69
Why is the arrangement of acetylcholine receptors and sodium channels important?
This arrangement is crucial for signal transmission at the neuromuscular junction facilitating communication between nerve and muscle.
70
Describe the structure of an acetylcholine receptor. What is its molecular weight?
Each acetylcholine receptor is a protein complex with a molecular weight of approximately 275000. It consists of five subunit proteins: two alpha proteins one beta one delta and one gamma protein.
71
What is the composition of acetylcholine receptors in fetal versus adult muscle?
In fetal muscle the receptor complex has a gamma protein. In adult muscle the gamma protein is substituted by an epsilon protein.
72
What is the role of the acetylcholine molecules in channel opening?
Binding of two acetylcholine molecules to the two alpha subunits of the receptor induces a conformational change which leads to the opening of the channel.
73
What occurs when acetylcholine binds to the receptor?
Binding of acetylcholine triggers a conformational change in the receptor resulting in the opening of the channel.
74
What is the diameter of the channel when it opens?
When the channel opens it has a diameter of about 0.65 nanometers.
75
What is the significance of the subunit structure of the acetylcholine receptor?
The specific arrangement of the five subunits allows for selective binding of acetylcholine and the opening of the ion channel which is essential for neurotransmission.
76
What type of ion channels are present in the postsynaptic membrane?
The postsynaptic membrane contains acetylcholine receptors and voltage-gated sodium channels both of which play roles in action potential generation.
77
Explain the concept of conformational change in the context of acetylcholine receptors. What triggers it?
Conformational change refers to the alteration in the structure of the receptor upon binding with acetylcholine which is triggered when two acetylcholine molecules bind to the alpha subunits allowing the ion channel to open.
78
What are the important positive ions mentioned in the passage?
The important positive ions mentioned in the passage are sodium (Na) potassium (K) and calcium (Ca2+).
79
What negative ion is mentioned in the passage?
The negative ion mentioned in the passage is chloride (Cl-).
80
What do patch clamp studies reveal about sodium ion transmission?
Patch clamp studies reveal that sodium ion channels can transmit between 15000 to 30000 sodium ions in 1 millisecond when opened.
81
Why are negative ions repelled in the ion channels as mentioned in the passage?
Negative ions are repelled by the negative charges within the channel mouth preventing their transmission through the channel.
82
What is the neuromuscular junction?
The neuromuscular junction is the synapse or junction between a motor neuron and a skeletal muscle fiber where neurotransmission occurs to stimulate muscle contraction.
83
In the context of muscle contraction what is acetylcholine (ACh)?
Acetylcholine (ACh) is a neurotransmitter that binds to receptor sites on the muscle fiber membrane at the neuromuscular junction leading to the generation of an end-plate potential.
84
What is an end-plate potential?
An end-plate potential is a depolarization of the muscle fiber membrane caused by the binding of acetylcholine which may lead to the generation of a muscle action potential.
85
What happens after the generation of an end-plate potential?
After the generation of an end-plate potential if the potential is strong enough it triggers a muscle action potential which leads to muscle contraction.
86
What do the letters A B and C represent in the graph of end-plate potentials?
In the graph potential B represents a normal end-plate potential that elicits an action potential while potentials A and C are weaker and do not result in an action potential.
87
What is the significance of ion channels in muscle excitation?
Ion channels are crucial for muscle excitation as they regulate the flow of ions across the muscle membrane which is essential for generating electrical signals (action potentials) that lead to muscle contraction.
88
What is the result of a weakened end plate potential in a curarized muscle?
A weakened end plate potential recorded in a curarized muscle is too weak to elicit an action potential.
89
How does the normal end plate potential differ from weakened potentials?
A normal end plate potential is strong enough to elicit a muscle action potential while weakened potentials do not produce this effect.
90
What effect does botulinum toxin have on end plate potentials?
Botulinum toxin decreases the release of acetylcholine resulting in a weakened end plate potential that is also too weak to elicit a muscle action potential.
91
What is the role of acetylcholine in muscle action potentials?
Acetylcholine is released into the synaptic space and activates acetylcholine receptors which are crucial for eliciting muscle action potentials.
92
What happens to acetylcholine in the synaptic space?
Once released into the synaptic space acetylcholine is rapidly destroyed by the enzyme acetylcholinesterase.
93
Where is acetylcholinesterase predominantly located?
Acetylcholinesterase is mainly located in the spongy layer of fine connective tissue that fills the synaptic space between the presynaptic nerve terminal and the postsynaptic muscle membrane.
94
What happens to acetylcholine that diffuses out of the synaptic space?
Acetylcholine that diffuses out of the synaptic space is no longer available to act on acetylcholine receptors.
95
Illustrate the importance of the acetylcholinesterase enzyme in neuromuscular junctions.
Acetylcholinesterase quickly breaks down acetylcholine in the synaptic cleft ensuring that muscle activation is tightly regulated and preventing continuous stimulation of the muscle.
96
What does Figure 7-4 illustrate about end plate potentials?
Figure 7-4 illustrates the differences in end plate potentials including a weakened end plate potential in a curarized muscle a normal end plate potential that elicits a muscle action potential and a weakened end plate potential caused by botulinum toxin.
97
Define end plate potential (EPP).
End plate potential (EPP) refers to the depolarization of the postsynaptic membrane potential due to the binding of acetylcholine released from the presynaptic neuron which can lead to an action potential if it reaches the threshold.
98
What is the role of acetylcholine in muscle fiber contraction?
Acetylcholine binds to the acetylcholine-gated channels on the muscle fiber membrane causing a conformational change that opens the channel. This allows sodium ions to enter the muscle fiber which excites the muscle fibers and triggers contraction.
99
Describe the states of the acetylcholine-gated channel as shown in Figure 7-3.
A) Closed state: The channel is not open preventing ion flow. B) Open state: After acetylcholine attaches the channel opens permitting sodium ions to enter the muscle fiber.
100
Why do sodium ions flow through acetylcholine-gated channels more than other ions?
Sodium ions flow through the channels more than other ions because there are only two positive ions in large concentrations: sodium in extracellular fluid and potassium in intracellular fluid. Additionally the negative membrane potential of -80 to -90 millivolts attracts sodium ions into the fiber while preventing potassium efflux.
101
What is the significance of the negative charges at the channel mouth of the acetylcholine-gated channel?
The negative charges at the channel mouth prevent the passage of negative ions such as chloride ions allowing for a selective flow of positive ions like sodium.
102
What is the typical membrane potential of a muscle fiber prior to activation?
The typical membrane potential of a muscle fiber prior to activation is between -80 to -90 millivolts.
103
Explain the movement of sodium and potassium ions during muscle fiber activation.
During activation sodium ions flow into the muscle fiber through open acetylcholine-gated channels due to the strong electrochemical gradient. The negative potential inside the fiber attracts the positively charged sodium ions while simultaneously preventing potassium ions from flowing out.
104
What are the two key positive ions involved in muscle fiber excitability and where are they primarily located?
The two key positive ions are sodium ions (Na+) which are present in high concentrations in the extracellular fluid and potassium ions (K+) which are present in high concentrations in the intracellular fluid.
105
What happens to the membrane potential as sodium ions enter the muscle fiber?
As sodium ions enter the muscle fiber the membrane potential becomes less negative (depolarization) which can lead to further actions potentials if the threshold is reached.
106
In terms of ion concentrations why is the acetylcholine-gated channel selective toward sodium ions?
The acetylcholine-gated channel is selective toward sodium ions primarily due to their high extracellular concentration compared to other ions which favors their rapid influx when the channel opens.
107
What is the effect of opening acetylcholine-gated channels in muscle fibers?
Opening acetylcholine-gated channels allows sodium ions (Na+) to flow into the inside of the muscle fiber carrying positive charges with them.
108
What is generated inside the muscle fiber when sodium ions enter due to acetylcholine-gated channel opening?
The entry of sodium ions creates a local positive potential change inside the muscle fiber membrane known as the end plate potential.
109
What is the typical change in membrane potential caused by the end plate potential?
The end plate potential typically causes a change in membrane potential of about 50 to 75 millivolts.
110
What is the result of the end plate potential in terms of muscle fiber depolarization?
The end plate potential normally causes sufficient depolarization to open neighboring voltage-gated sodium channels.
111
What happens after voltage-gated sodium channels open in response to the end plate potential?
When voltage-gated sodium channels open this allows even greater sodium ion inflow leading to the initiation of an action potential.
112
What is the ultimate effect of the action potential that spreads along the muscle membrane?
The action potential that spreads along the muscle membrane ultimately causes muscle contraction.
113
What threshold change in membrane potential is necessary to initiate the action potential?
A sudden increase in nerve membrane potential of more than 20 to 30 millivolts is necessary to initiate the action potential.
114
What is the significance of the end plate potential in the context of excitation-contraction coupling in skeletal muscle fibers?
The end plate potential is crucial for exciting the muscle fiber and triggering the cascade of events that lead to muscle contraction.
115
How does the influx of sodium ions during the end plate action affect the muscle fiber's environment?
The influx of sodium ions increases the positive charge inside the muscle fiber contributing to depolarization.
116
What role does acetylcholine play in the process of muscle contraction?
Acetylcholine binds to its receptors on muscle fibers leading to the opening of sodium-gated channels and initiating the process of muscle contraction.
117
What are millivolts in the context of muscle fiber membrane action potentials?
Millivolts refer to the electrical potential that is sufficient to initiate the opening of sodium channels leading to the generation of an action potential in muscle fibers.
118
What are end plate potentials (EPPs)?
End plate potentials (EPPs) are localized changes in membrane voltage at the neuromuscular junction which occur when neurotransmitters bind to receptors on the muscle fiber membrane.
119
What is the significance of Figure 7-4 regarding action potentials?
Figure 7-4 illustrates how different end plate potentials (A B and C) can elicit varying responses in muscle fibers showcasing that EPPs A and C are insufficient to trigger an action potential while EPP B is strong enough to do so.
120
Out of the three end plate potentials shown in Figure 7-4 which one is strong enough to elicit an action potential?
End plate potential B is strong enough to elicit an action potential by causing sufficient opening of sodium channels.
121
What does it mean that end plate potentials A and C produced weak local voltage changes?
End plate potentials A and C while not strong enough to elicit an action potential still resulted in minor voltage changes in the muscle fiber that do not reach the necessary threshold for action potential initiation.
122
What is meant by the 'safety factor' in the context of the neuromuscular junction?
The safety factor refers to the reliability of transmission at the neuromuscular junction where typically each nerve impulse produces a significantly larger end plate potential than needed to stimulate the muscle fiber indicating a high safety factor.
123
How much EPP is typically produced compared to what is required to stimulate the muscle fiber?
Ordinarily each impulse that arrives at the neuromuscular junction causes about three times as much end plate potential as that required to stimulate the muscle fiber.
124
What happens if the nerve fiber is stimulated at high rates in relation to neuromuscular transmission?
Stimulation of the nerve fiber at high rates can lead to fatigue at the neuromuscular junction which may diminish the end plate potential and compromise the safety factor for transmitting signals to the muscle fibers.
125
What role do sodium channels play in the generation of action potentials at the neuromuscular junction?
Sodium channels open in response to depolarization caused by end plate potentials allowing sodium ions to enter the muscle fiber which further depolarizes the membrane and can lead to the initiation of an action potential.
126
Describe the relationship between nerve impulses and end plate potentials in healthy neuromuscular junction functioning.
In a healthy neuromuscular junction each nerve impulse results in a significantly greater end plate potential ensuring that the signal is effectively transmitted to the muscle fibers maintaining muscle function.
127
What is the effect of stimulating a neuromuscular junction greater than 100 times per second for several minutes?
It may diminish the number of acetylcholine vesicles to such an extent that impulses fail to pass into the muscle fiber resulting in a condition known as fatigue of the neuromuscular junction.
128
What is defined as fatigue of the neuromuscular junction?
Fatigue of the neuromuscular junction refers to the situation where impulses fail to pass into the muscle fiber due to the depletion of acetylcholine vesicles resulting from excessive stimulation.
129
How is neuromuscular junction fatigue related to central nervous system fatigue?
The fatigue of the neuromuscular junction is similar to the fatigue of synapses in the central nervous system which occurs when synapses are over-excited.
130
Under what conditions does measurable fatigue of the neuromuscular junction occur?
Measurable fatigue of the neuromuscular junction occurs rarely and primarily at the most exhausting levels of muscle activity.
131
What is acetylcholine and where is it formed?
Acetylcholine is a neurotransmitter formed in the cell body of the motoneuron in the spinal cord.
132
What is the size of the vesicles that store acetylcholine?
The vesicles that store acetylcholine are about 40 nanometers in size.
133
How are acetylcholine vesicles transported to the neuromuscular junction?
The vesicles are transported by axoplasm that streams through the core of the axon from the central cell body in the spinal cord to the neuromuscular junction.
134
What role does the Golgi apparatus play in acetylcholine vesicle formation?
The Golgi apparatus in the cell body of the motoneuron is responsible for forming small vesicles that contain acetylcholine.
135
What happens to acetylcholine vesicles during high-frequency stimulation?
During high-frequency stimulation the number of acetylcholine vesicles may become depleted leading to failure in transmitting impulses to the muscle fibers.
136
What is the approximate number of acetylcholine vesicles that collect in the nerve terminals of a single skeletal muscle end plate?
About 300000 small vesicles collect in the nerve terminals of a single skeletal muscle end plate.
137
Where is acetylcholine synthesized in a nerve fiber?
Acetylcholine is synthesized in the cytosol of the nerve fiber terminal.
138
How is acetylcholine stored in vesicles?
Acetylcholine is transported through the membranes of the vesicles to their interior where it is stored in highly concentrated form with about 10000 molecules of acetylcholine in each vesicle.
139
What effect does the arrival of an action potential have on the calcium channels in the nerve terminal?
The arrival of an action potential opens many calcium channels in the membrane of the nerve terminal leading to an increase in calcium ion concentration.
140
By how much does the calcium ion concentration increase inside the terminal membrane when an action potential arrives?
The calcium ion concentration inside the terminal membrane increases about 100-fold.
141
How does the increase in calcium ion concentration affect the rate of fusion of acetylcholine vesicles with the terminal membrane?
The increase in calcium ion concentration raises the rate of fusion of the acetylcholine vesicles with the terminal membrane about 10000-fold.
142
What process occurs due to the fusion of acetylcholine vesicles with the terminal membrane?
The fusion causes many of the vesicles to rupture allowing exocytosis of acetylcholine into the synaptic space.
143
How many vesicles typically rupture with each action potential?
About 125 vesicles usually rupture with each action potential.
144
What is the function of exocytosis in the context of nerve terminals?
Exocytosis releases acetylcholine into the synaptic space allowing it to transmit signals to the muscle or other neurons.
145
What role do voltage-gated calcium channels play in neurotransmitter release?
Voltage-gated calcium channels open in response to an action potential causing an influx of calcium ions that triggers the fusion and exocytosis of neurotransmitter vesicles.
146
What is the role of acetylcholinesterase in neurotransmission?
Acetylcholinesterase splits acetylcholine into acetate ion and choline facilitating the termination of neurotransmission by removing acetylcholine from the synaptic cleft.
147
How quickly does the split of acetylcholine by acetylcholinesterase occur?
The split of acetylcholine by acetylcholinesterase occurs within a period of 5 to 10 milliseconds.
148
What happens to choline after it is split from acetylcholine?
Choline is actively reabsorbed into the neural terminal to be re-used for the synthesis of new acetylcholine.
149
How many vesicles are available in the nerve ending for nerve to muscle impulses?
The number of vesicles available in the nerve ending is only sufficient to allow transmission of a few thousand nerve to muscle impulses.
150
What is required for the continued function of the neuromuscular junction?
For continued function of the neuromuscular junction new vesicles need to be re-formed rapidly.
151
What structural change happens in the nerve ending after an action potential?
Coated pits appear in the terminal nerve membrane caused by contractile proteins especially clathrin which are attached to the membrane in the areas of the original vesicles.
152
How long does it take for new vesicles to form after an action potential?
Within about 20 seconds after the action potential the pits break away to the interior of the membrane thus forming new vesicles.
153
What is the function of clathrin in the nerve terminal?
Clathrin is a contractile protein that helps in the formation of new vesicles by causing the coated pits to break away from the membrane.
154
What occurs immediately after the formation of new vesicles?
Within another few seconds after vesicle formation acetylcholine is transported to the new vesicles for subsequent neurotransmission.
155
What compounds have effects similar to acetylcholine on muscle fibers?
Methacholine carbachol and nicotine.
156
How do methacholine carbachol and nicotine differ from acetylcholine?
These drugs are not destroyed by cholinesterase or are destroyed at a much slower rate allowing their action to last for many minutes to several hours.
157
What is the mechanism by which methacholine carbachol and nicotine exert their effects on muscle fibers?
They cause localized depolarization of the muscle fiber membrane at the motor end plate where acetylcholine receptors are located.
158
What is the result of depolarization areas created by these drugs on muscle contraction?
These depolarized areas leak ions initiating a new action potential each time the muscle fiber recovers from a contraction which can lead to muscle spasms.
159
What effect do drugs that enhance transmission at the neuromuscular junction have on muscle contraction?
They stimulate the muscle fiber often leading to prolonged contraction or spasms.
160
What role does cholinesterase play in the action of acetylcholine at the neuromuscular junction?
Cholinesterase breaks down acetylcholine terminating its action rapidly after muscle contraction.
161
Why is the prolonged action of drugs like methacholine and carbachol significant for muscle function?
Their prolonged action can result in sustained muscle contraction or spasms affecting normal muscle function.
162
What is the effect of drugs that block transmission at the neuromuscular junction?
They inhibit muscle contraction by preventing the action of acetylcholine at its receptors.
163
What are the potential clinical implications of drugs that stimulate or block transmission at the neuromuscular junction?
They can be used to treat various conditions related to neuromuscular transmission issues such as myasthenia gravis or to induce paralysis during surgical procedures.
164
How does the leaking of ions from depolarized areas affect muscle fibers?
It leads to the initiation of new action potentials causing the muscle fiber to contract repeatedly.
165
What is the primary function of acetylcholinesterase in the synapses?
Acetylcholinesterase hydrolyzes acetylcholine in the synapses terminating the action of acetylcholine and allowing muscle relaxation after stimulation.
166
Name three drugs that inactivate acetylcholinesterase.
The three drugs that inactivate acetylcholinesterase are neostigmine physostigmine and diisopropyl fluorophosphate.
167
How do neostigmine and physostigmine affect acetylcholinesterase?
Neostigmine and physostigmine bind to acetylcholinesterase and inactivate it preventing the hydrolysis of acetylcholine leading to an accumulation of acetylcholine in the synapse.
168
What happens to muscle fibers when acetylcholine accumulates due to acetylcholinesterase inactivation?
When acetylcholine accumulates it stimulates muscle fibers repetitively causing muscle spasms or even paralysis due to continuous stimulation.
169
What is a potential lethal outcome of acetylcholinesterase inactivation?
A potential lethal outcome is laryngeal spasm which can lead to smothering and death due to respiratory failure.
170
How long do neostigmine and physostigmine remain effective in inactivating acetylcholinesterase?
Neostigmine and physostigmine inactivate acetylcholinesterase for several hours before they are displaced and allow the esterase to become active again.
171
What differentiates diisopropyl fluorophosphate from neostigmine and physostigmine in terms of duration of action?
Diisopropyl fluorophosphate inactivates acetylcholinesterase for weeks making it significantly more lethal compared to neostigmine and physostigmine which have effects lasting only hours.
172
What type of compound is diisopropyl fluorophosphate and what is its significance?
Diisopropyl fluorophosphate is a powerful nerve gas poison; its long duration of action inactivating acetylcholinesterase makes it particularly lethal.
173
What can excessive accumulation of acetylcholine lead to at the neuromuscular junction?
Excessive accumulation of acetylcholine at the neuromuscular junction can lead to muscle fatigue spasms and potentially paralysis.
174
What is the mechanism of action for drugs that block transmission at the neuromuscular junction?
Drugs that block transmission at the neuromuscular junction may work by preventing the release of acetylcholine blocking acetylcholine receptors or inhibiting acetylcholinesterase leading to disrupted communication between nerves and muscles.
175
What are curariform drugs?
Curariform drugs are a group of drugs that can prevent the passage of impulses from the nerve endings into the muscle.
176
How does D-tubocurarine affect muscle contraction?
D-tubocurarine blocks the action of acetylcholine on muscle fiber acetylcholine receptors which prevents an adequate increase in permeability of the muscle membrane channels necessary to initiate an action potential.
177
What is the role of acetylcholine in neuromuscular transmission?
Acetylcholine is a neurotransmitter that transmits signals from nerve fibers to muscle fibers by binding to acetylcholine receptors on the muscle membrane facilitating muscle contraction.
178
What is myasthenia gravis?
Myasthenia gravis is an autoimmune disease characterized by muscle weakness resulting from the inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers.
179
What is the prevalence of myasthenia gravis?
Myasthenia gravis occurs in about 1 in every 20000 persons.
180
What causes muscle weakness in myasthenia gravis?
Muscle weakness in myasthenia gravis is caused by antibodies that attack and block or destroy acetylcholine receptors at the neuromuscular junction.
181
What type of disease is myasthenia gravis considered to be?
Myasthenia gravis is considered to be an autoimmune disease.
182
What is the function of acetylcholine receptors at the neuromuscular junction?
Acetylcholine receptors at the neuromuscular junction bind acetylcholine leading to an increase in the permeability of the muscle membrane channels which is essential for initiating action potentials and muscle contraction.
183
What is the consequence of antibodies attacking acetylcholine receptors in patients with myasthenia gravis?
The consequence is diminished signal transmission from nerves to muscles leading to muscle weakness and fatigue.
184
What role do neuromuscular junctions play in muscle contraction?
Neuromuscular junctions play a crucial role in transmitting signals from motor neurons to skeletal muscle fibers which is essential for muscle contraction.
185
What happens at the postsynaptic neuromuscular junction during muscle fiber depolarization?
At the postsynaptic neuromuscular junction end plate potentials occur in muscle fibers. However these potentials are mostly too weak to initiate the opening of voltage-gated sodium channels resulting in a failure of muscle fiber depolarization.
186
What can happen if the disease affecting the neuromuscular junction is severe enough?
If the disease affecting the neuromuscular junction is severe enough the patient may die from respiratory failure due to severe weakness of the respiratory muscles.
187
How can the symptoms of certain neuromuscular diseases be ameliorated temporarily?
The symptoms can usually be ameliorated for several hours by administering neostigmine or another anticholinesterase drug which allows larger than normal amounts of acetylcholine to accumulate in the synaptic space.
188
What is the effect of administering neostigmine on patients affected by neuromuscular diseases?
Within minutes of administering neostigmine some patients can begin to function almost normally; however a new dose is required a few hours later as the effects wear off.
189
How do action potentials in skeletal muscle fibers relate to those in nerve fibers?
Almost everything discussed regarding the initiation and conduction of action potentials in nerve fibers applies equally to skeletal muscle fibers though there are quantitative differences.
190
What is a muscle action potential?
A muscle action potential is an electrical impulse that triggers muscle contraction similar in mechanics to action potentials in nerve fibers but with quantitative differences in properties.
191
What role does acetylcholine play in muscle fiber depolarization?
Acetylcholine is a neurotransmitter that when released at the neuromuscular junction binds to receptors on muscle fibers to generate end plate potentials which are necessary for muscle fiber depolarization.
192
What is the consequence of weak end plate potentials in muscle fibers?
Weak end plate potentials are insufficient to trigger the opening of voltage-gated sodium channels therefore preventing muscle depolarization and contraction.
193
Which ion is primarily involved in depolarization during the muscle action potential?
Sodium ions (Na+) are primarily responsible for depolarization during the muscle action potential.
194
What is the effect of anticholinesterase drugs on muscle function?
Anticholinesterase drugs like neostigmine increase the accumulation of acetylcholine in the synaptic cleft enhancing neurotransmission and improving muscle function temporarily.
195
What is the resting membrane potential in skeletal muscle fibers?
The resting membrane potential in skeletal muscle fibers is about -80 to -90 millivolts which is 10 to 20 millivolts more negative than in neurons.
196
How long is the duration of the action potential in skeletal muscle?
The duration of the action potential in skeletal muscle ranges from 1 to 5 milliseconds which is about five times longer than that of large myelinated nerves.
197
What is the velocity of conduction in skeletal muscle fibers?
The velocity of conduction in skeletal muscle fibers is 3 to 5 milliseconds approximately one third the velocity of conduction in large myelinated nerve fibers that excite skeletal muscle.
198
How do action potentials spread to the interior of a muscle fiber?
Action potentials spread to the interior of muscle fibers through transverse tubules (T-tubules) which allow the current to penetrate deeply into the muscle fiber for maximum muscle contraction.
199
Why is it important for action potentials to penetrate deeply into skeletal muscle fibers?
Deep penetration of action potentials into skeletal muscle fibers is important because maximum muscle contraction requires the current to reach the vicinity of the separate myofibrils.
200
What role do T-tubules play in muscle contraction?
T-tubules facilitate the transmission of action potentials deep into skeletal muscle fibers ensuring adequate activation of the myofibrils for effective muscle contraction.
201
How do the resting membrane potentials of skeletal fibers and neurons compare?
The resting membrane potential of skeletal fibers is approximately 10 to 20 millivolts more negative than that of neurons which is typically around -70 to -80 millivolts.
202
In terms of action potential duration how do skeletal muscles and large myelinated nerves compare?
Skeletal muscle action potentials last 1 to 5 milliseconds while those in large myelinated nerves are significantly shorter resulting in skeletal muscle having a longer action potential duration.
203
What is the significance of the conduction velocity in skeletal muscle?
The conduction velocity of 3 to 5 milliseconds in skeletal muscle is significant as it reflects how quickly action potentials can propagate along the muscle fibers influencing the timing and coordination of muscle contractions.
204
What is excitation-contraction coupling?
Excitation-contraction coupling is the physiological process where an electrical signal (action potential) in a muscle fiber leads to muscle contraction. This process involves the release of calcium ions from the sarcoplasmic reticulum in response to the action potential propagating through the T tubules.
205
Describe the structure and function of T tubules in muscle fibers.
T tubules or transverse tubules are small tubular structures that run perpendicular to the myofibrils within a muscle fiber. They originate from the cell membrane and penetrate through the muscle fiber to connect with the extracellular fluid. Their primary function is to conduct action potentials from the surface of the muscle cell deep into the muscle ensuring that the signal for contraction reaches all areas of the muscle fiber effectively.
206
What role do calcium ions play in muscle contraction?
Calcium ions released from the sarcoplasmic reticulum in response to action potentials are crucial for muscle contraction. These ions bind to troponin causing a conformational change that moves tropomyosin away from the binding sites on actin filaments allowing for cross-bridge formation between actin and myosin and resulting in contraction.
207
How do T tubules communicate with the sarcoplasmic reticulum?
T tubules branch and interlace among myofibrils and are closely associated with the sarcoplasmic reticulum. When an action potential travels down the T tubules it triggers the release of calcium ions from the cisternae of the sarcoplasmic reticulum into the cytosol surrounding the myofibrils thus facilitating muscle contraction.
208
What is the significance of the T tubule-sarcoplasmic reticulum system in muscle contraction?
The T tubule-sarcoplasmic reticulum system is significant because it ensures that the contraction signal is transmitted efficiently and quickly to all parts of the muscle fiber. This system allows for synchronized contraction of muscle fibers which is essential for the overall function of muscles.
209
Explain the relationship between action potentials and muscle contraction.
Action potentials are electrical signals generated by neurons that when they reach the muscle fiber membrane cause depolarization. This depolarization travels along the T tubules triggering the release of calcium ions from the sarcoplasmic reticulum which are critical for initiating the biochemical processes that lead to muscle contraction.
210
What happens to T tubules during muscle contraction?
During muscle contraction T tubules propagate the action potential and facilitate the rapid release of calcium ions from the sarcoplasmic reticulum. Their ability to reach deep into the muscle fiber ensures that the contraction occurs uniformly throughout the muscle rather than just on the surface.
211
Describe the overall process of muscle contraction starting from the action potential.
The overall process begins when an action potential reaches the muscle fiber membrane causing depolarization. This depolarization is transmitted through T tubules to the sarcoplasmic reticulum causing the release of calcium ions. The calcium ions then bind to troponin leading to the movement of tropomyosin and exposure of binding sites on actin. Myosin heads then attach to these sites forming cross-bridges and the sliding filament mechanism occurs resulting in muscle contraction.
212
What are T tubules and their function in muscle fibers?
T tubules or transverse tubules are internal extensions of the muscle fiber cell membrane. They surround the muscle fibers and contain extracellular fluid in their lumens. Their main function is to conduct electrical signals (action potentials) deep into the interior of the muscle fiber which is essential for triggering muscle contraction.
213
How do action potentials affect T tubules?
When an action potential spreads over the muscle fiber membrane it also spreads along the T tubules. This results in a change in electrical potential that triggers muscle contraction by eliciting electrical currents surrounding the T tubules.
214
What is the role of the sarcoplasmic reticulum in muscle contraction?
The sarcoplasmic reticulum (SR) has two major parts: terminal cisternae and longitudinal tubules. It plays a critical role in muscle contraction by storing calcium ions in high concentrations and releasing them upon stimulation which is necessary for the contraction process.
215
What are the two major components of the sarcoplasmic reticulum?
The sarcoplasmic reticulum consists of two major components: 1) terminal cisternae which are large chambers that abut the T tubules and 2) long longitudinal tubules that surround the surfaces of contracting myofibrils.
216
What happens to calcium ions in the sarcoplasmic reticulum when an action potential occurs?
When an action potential occurs in the adjacent T tubules it triggers the release of calcium ions from the vesicular tubules of the sarcoplasmic reticulum. This release of calcium ions is critical for muscle contraction.
217
Describe the structure of the sarcoplasmic reticulum.
The sarcoplasmic reticulum is a highly organized structure that surrounds the myofibrils in muscle fibers. It consists of terminal cisternae which are large dilated areas close to the T tubules and interconnected longitudinal tubules that extend throughout the muscle fiber.
218
Why is calcium ion concentration important in sarcoplasmic reticulum?
Calcium ion concentration is essential in the sarcoplasmic reticulum because it allows for rapid release of calcium during muscle activation. High concentrations of calcium ions facilitate the binding to troponin which leads to the contraction of the muscle fibers.
219
Explain the relationship between T tubules and the sarcoplasmic reticulum.
T tubules are closely associated with the sarcoplasmic reticulum providing a direct pathway for action potentials to trigger the release of calcium ions. The proximity of T tubules to the terminal cisternae of the SR enables synchronized contraction of all myofibrils within a muscle fiber.
220
What is the significance of the electrical currents surrounding T tubules in muscle contraction?
The electrical currents surrounding T tubules play a crucial role in eliciting muscle contraction by facilitating the release of calcium from the sarcoplasmic reticulum ultimately allowing for interaction between actin and myosin filaments during the contraction process.
221
What triggers the release of calcium ions in the muscle contraction process?
The release of calcium ions is triggered by the depolarization of the T tubules due to an action potential which results in a cascade of events leading to calcium release from the sarcoplasmic reticulum.
222
What is the role of T tubules in muscle contraction?
T tubules allow action potentials to rapidly penetrate into the muscle fiber triggering the release of calcium ions from the sarcoplasmic reticulum (SR) during muscle contraction.
223
What happens when an action potential reaches the T tubule?
The action potential causes current flow into the sarcoplasmic reticular cisternae which abut the T tubule triggering calcium release essential for muscle contraction.
224
What are dihydropyridine receptors?
Dihydropyridine receptors are voltage-sensitive receptors located in the T tubules that sense the voltage change due to action potentials and are linked to calcium release channels.
225
What are ryanodine receptors?
Ryanodine receptor channels are calcium release channels located in the sarcoplasmic reticulum that open in response to activation by dihydropyridine receptors.
226
What initiates the release of calcium ions during muscle contraction?
The activation of dihydropyridine receptors triggers the opening of ryanodine receptors in the sarcoplasmic reticulum resulting in the release of calcium ions into the sarcoplasm.
227
What is the duration of calcium ion release through ryanodine receptors?
The ryanodine receptors remain open for a few milliseconds allowing calcium ions to be released into the sarcoplasm.
228
Where do the calcium ions go after being released?
Calcium ions diffuse among the myofibrils where they bind to troponin leading to muscle contraction.
229
How does calcium contribute to muscle contraction?
Calcium binds to troponin causing a conformational change that allows tropomyosin to move away from the actin binding sites enabling cross-bridge formation between actin and myosin.
230
What is the function of calcium pumps in muscle cells?
Calcium pumps remove calcium ions from the myofibrillar fluid after contraction which helps to relax the muscle and restore the calcium ion concentration in the sarcoplasmic reticulum.
231
What happens after calcium ions are removed from the sarcoplasm?
Once calcium ions are removed muscle contraction stops and the muscle fiber relaxes.
232
What is the role of the calcium pump located in the sarcoplasmic reticulum?
The calcium pump actively transports calcium ions away from the myofibrils and into the sarcoplasmic reticulum maintaining a high concentration of calcium within the reticulum which is crucial for muscle contraction.
233
How does the transverse tubule system communicate with the muscle fiber and the rest of the cell?
Transverse tubules (T tubules) directly communicate with the external environment of the cell membrane. They are deep invaginations that allow the action potential to penetrate into the muscle fiber facilitating the rapid transmission of electrical signals.
234
What is the significance of T tubules in skeletal muscle compared to frog and mammalian heart muscle?
In skeletal muscle there are two T tubules per sarcomere located at the A-I band junctions whereas in frog muscle there is one T tubule per sarcomere at the Z disk. This arrangement is crucial for ensuring efficient signaling for muscle contractions.
235
Describe the triad structure in muscle fibers.
The triad consists of one T tubule and two terminal cisternae of the sarcoplasmic reticulum. This structure is essential for coupling the electrical signals from the T tubules to the calcium release required for muscle contraction.
236
What are the components of a typical sarcomere in muscle tissue?
A typical sarcomere consists of the Z disk (Z line) A band I band H zone and M line. The A band contains thick filaments (myosin) while the I band contains thin filaments (actin). The H zone is the area within the A band that only contains thick filaments.
237
What is the function of mitochondria in muscle cells?
Mitochondria in muscle cells generate ATP through aerobic respiration supplying the energy necessary for muscle contraction.
238
Explain the function of the sarcolemma in muscle cells.
The sarcolemma is the plasma membrane of muscle fibers and it surrounds the cell. It plays a critical role in conducting electrical impulses and propagating action potentials necessary for muscle contraction.
239
What is the significance of the Z disk in muscle contraction?
The Z disk serves as the anchoring point for thin filaments (actin) in the sarcomere and during contraction the sarcomere shortens as the Z disks move closer together enabling muscle fiber shortening and force generation.
240
What happens to calcium ions after muscle contraction?
After muscle contraction calcium ions are pumped back into the sarcoplasmic reticulum by the calcium pump allowing muscle fibers to relax and preventing continuous contraction.
241
What is the A band composed of in muscle fibers and why is it important?
The A band contains both thick (myosin) and thin (actin) filaments and it is important because it is the region of muscle contraction where cross-bridge cycling occurs leading to force generation.
242
Describe the structure and function of the terminal cisternae in muscle cells.
The terminal cisternae are enlarged areas of the sarcoplasmic reticulum located adjacent to T tubules. They store calcium ions and release them in response to action potentials initiating muscle contraction.
243
What is the role of the H zone during muscle contraction?
The H zone is the area in the A band where only thick filaments (myosin) are present. During contraction the H zone decreases in width as the actin filaments slide over the myosin filaments.
244
What is SERCA and its role in muscle contraction?
SERCA stands for Sarcoplasmic Reticulum Ca2+ ATPase. It is a calcium pump located in the sarcoplasmic reticulum that actively transports calcium ions (Ca2+) back into the sarcoplasmic tubules helping to concentrate them about 10000-fold. This process is crucial for muscle relaxation and for maintaining low levels of calcium in the cytosol during the resting state.
245
What is the significance of calsequestrin in muscle cells?
Calsequestrin is a calcium-binding protein found in the sarcoplasmic reticulum that can bind up to 40 calcium ions for each molecule. Its primary role is to store calcium ions allowing for rapid release during muscle contraction while maintaining an appropriate concentration gradient that is necessary for effective muscle function.
246
What is the normal resting concentration of calcium ions in the cytosol of muscle cells?
The normal resting state concentration of calcium ions in the cytosol that bathes the myofibrils is approximately 10^-7 molar. This low concentration is not sufficient to trigger muscle contraction.
247
How does the troponin-tropomyosin complex affect muscle contraction?
The troponin-tropomyosin complex inhibits the binding sites on actin filaments when calcium concentrations are low. This keeps the muscle in a relaxed state. When calcium levels increase significantly the complex undergoes a conformational change allowing myosin heads to bind to actin and initiate muscle contraction.
248
What is the effect of calcium ion concentration during full excitation of the T tubule and sarcoplasmic reticulum system?
During full excitation the concentration of calcium ions in the myofibrillar fluid can increase to as high as 2 x 10^-4 molar which represents a 500-fold increase from the resting state. This elevated concentration is approximately 10 times the level required to cause maximum muscle contraction.
249
What happens immediately after calcium ions are released during muscle contraction?
Immediately after calcium ions are released into the cytosol resulting in muscle contraction the calcium pump (SERCA) begins to actively transport calcium back into the sarcoplasmic reticulum facilitating muscle relaxation and returning calcium concentrations to resting levels.
250
What is the overall mechanism of muscle contraction in relation to calcium ion dynamics?
The mechanism of muscle contraction involves the release of calcium ions from the sarcoplasmic reticulum into the cytosol which leads to the binding of calcium to troponin. This binding causes a conformational change in the troponin-tropomyosin complex exposing binding sites on actin for myosin heads thus enabling muscle contraction. Following contraction calcium is pumped back into the sarcoplasmic reticulum by SERCA for muscle relaxation.
251
Describe the calcium dynamics in muscle contraction including resting excited and relaxation states.
In the resting state calcium concentration in the cytosol is about 10^-7 molar preventing contraction due to the inhibitory action of the troponin-tropomyosin complex. Upon excitation calcium ions are released elevating the concentration up to 2 x 10^-4 molar which activates muscle contraction. After contraction SERCA pumps calcium back into the sarcoplasmic reticulum lowering the cytosolic calcium concentration back to resting levels for muscle relaxation.
252
What is the role of T tubules in muscle contraction?
T tubules are invaginations of the muscle cell membrane (sarcolemma) that allow for the rapid transmission of action potentials into the interior of the muscle fiber. They play a crucial role in facilitating the release of calcium ions from the sarcoplasmic reticulum in response to an electrical signal thus initiating the contraction process.
253
What is the duration of the calcium pulse in skeletal muscle fibers?
The total duration of the calcium pulse in skeletal muscle fiber lasts about 120 milliseconds although it may vary significantly among different fibers.
254
What is the duration of the calcium pulse in heart muscle?
In heart muscle the calcium pulse lasts about one-third of a second due to the long duration of the cardiac action potential.
255
What physiological event occurs during the calcium pulse?
Muscle contraction occurs during the calcium pulse.
256
How can sustained muscle contraction be maintained?
Sustained muscle contraction can be maintained by a series of calcium pulses initiated by continuous repetitive action potentials.
257
What is malignant hyperthermia?
Malignant hyperthermia is a serious condition in susceptible individuals triggered by exposure to certain anesthetics which can lead to a hypermetabolic crisis.
258
Which anesthetics are known to trigger malignant hyperthermia in susceptible individuals?
Anesthetics such as halothane isoflurane and succinylcholine are known to trigger malignant hyperthermia.
259
What genetic mutations are associated with an increased risk of malignant hyperthermia?
At least six genetic mutations particularly in the ryanodine receptor or dihydropyridine receptor genes have been shown to significantly increase susceptibility to malignant hyperthermia.
260
What is malignant hyperthermia and how does it relate to anesthesia?
Malignant hyperthermia is a pharmacogenetic disorder triggered by certain anesthetic agents resulting in a hypermetabolic state in skeletal muscle leading to a rapid increase in body temperature muscle rigidity and potentially fatal complications. The specific mechanisms are not completely understood but they are thought to involve abnormal calcium handling in muscle cells.
261
What is the role of the dihydropyridine (DHP) receptor in skeletal muscle excitation-contraction coupling?
The DHP receptor is a voltage-sensitive calcium channel located in the transverse tubule membrane of skeletal muscle. It undergoes a conformational change upon depolarization of the action potential which leads to the opening of the ryanodine receptor (RyR) channels in the sarcoplasmic reticulum allowing Ca²⁺ to flow into the cytoplasm to initiate muscle contraction.
262
Describe the process of excitation-contraction coupling in skeletal muscle.
Excitation-contraction coupling in skeletal muscle begins with an action potential that travels down the transverse tubule causing DHP receptors to undergo conformational changes. This opens the RyR channels in the sarcoplasmic reticulum allowing Ca²⁺ ions to diffuse into the sarcoplasm. The increased Ca²⁺ concentration initiates muscle contraction by interacting with troponin and tropomyosin on the actin filaments. During repolarization DHP receptors close the Ca²⁺ release channels and calcium is pumped back into the sarcoplasmic reticulum by SERCA (sarcoplasmic reticulum Ca²⁺ ATPase) facilitating muscle relaxation.
263
What is the function of calsequestrin in skeletal muscle?
Calsequestrin is a calcium-binding protein located within the sarcoplasmic reticulum that helps to store Ca²⁺ ions. It plays a key role in managing the concentration of Ca²⁺ in the sarcoplasmic reticulum allowing for rapid release of Ca²⁺ during muscle contraction while preventing excessive release that could lead to cellular damage.
264
What happens during the repolarization phase of muscle contraction?
During the repolarization phase the action potential diminishes leading to the conformational change of the DHP receptors that causes the closure of the RyR channels in the sarcoplasmic reticulum. Subsequently Ca²⁺ ions are pumped back into the sarcoplasmic reticulum by the SERCA pump decreasing the cytoplasmic Ca²⁺ concentration and allowing the muscle to relax.
265
What is the role of SERCA in muscle cells?
SERCA (Sarcoplasmic Endoplasmic Reticulum Calcium ATPase) is an enzyme that pumps Ca²⁺ ions from the cytoplasm back into the sarcoplasmic reticulum thus playing a crucial role in muscle relaxation. By actively transporting Ca²⁺ against its concentration gradient SERCA helps to restore low cytosolic Ca²⁺ levels post-contraction.
266
What are ryanodine receptors (RyR) and their significance in muscle contraction?
Ryanodine receptors (RyR) are calcium channels located on the membrane of the sarcoplasmic reticulum in muscle cells. Upon activation by the conformational change in the DHP receptors during muscle excitation they release stored Ca²⁺ into the cytoplasm leading to muscle contraction. RyRs are crucial in mediating calcium-induced calcium release which is essential for the strong contractions of skeletal muscles.
267
What is the role of calcium ions (Ca²⁺) in muscle contraction?
Calcium ions (Ca²⁺) are essential for muscle contraction as they bind to troponin causing a conformational change that moves tropomyosin away from actin's myosin-binding sites. This allows the myosin heads to attach to actin filaments initiating the power stroke that results in muscle contraction.
268
What is the function of SERCA in muscle physiology?
SERCA (sarcoplasmic reticulum Ca²⁺-ATPase) is an adenosine triphosphate-dependent calcium pump that transports calcium ions from the sarcoplasm back into the sarcoplasmic reticulum thereby helping to regulate calcium levels in muscle cells and facilitating muscle relaxation after contraction.
269
Describe the excitation-contraction coupling process in muscle cells.
Excitation-contraction coupling in muscle cells begins with an action potential generating an electrical signal across the sarcolemma (muscle cell membrane). This electrical signal triggers the release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum into the sarcoplasm. The increase in calcium concentration initiates muscle contraction by enabling actin and myosin filaments to interact. Following contraction SERCA pumps return Ca²⁺ back to the sarcoplasmic reticulum for muscle relaxation.
270
What role does ATP play in the function of SERCA?
ATP is required for the function of SERCA as it provides the energy necessary for the active transport of calcium ions from the sarcoplasm into the sarcoplasmic reticulum against their concentration gradient. This process is crucial for muscle relaxation and maintaining calcium homeostasis within the muscle cell.
271
What conditions can result from mutations affecting calcium ion channels in muscle cells?
Mutations that affect calcium ion channels in muscle cells can lead to conditions like malignant hyperthermia where there is uncontrolled influx of calcium ions from the sarcoplasmic reticulum into the intracellular space. This causes excessive muscle contraction increases metabolic rate generates excessive heat and can lead to cellular acidosis.
272
What is malignant hyperthermia and its link to muscle physiology?
Malignant hyperthermia is a life-threatening condition triggered by certain anesthetics or muscle relaxants in predisposed individuals often due to genetic mutations in calcium release channels. These mutations cause excessive release of calcium ions from the sarcoplasmic reticulum leading to uncontrolled muscle contractions and hypermetabolism which generates heat and can cause severe acidosis.
273
What are the consequences of sustained muscle contractions in the context of metabolic rate?
Sustained muscle contractions such as those seen in malignant hyperthermia greatly increase the metabolic rate of the muscle fibers. This heightened metabolism leads to a significant increase in heat production which can be harmful and may lead to complications such as cellular damage and metabolic derangements.
274
Explain the relationship between sarcolemma and action potentials in muscle contraction.
The sarcolemma is the cell membrane of muscle fibers that generates action potentials. When stimulated by a nerve impulse the sarcolemma depolarizes and generates an action potential that propagates along its surface. This change in membrane potential triggers the release of calcium from the sarcoplasmic reticulum leading to muscle contraction. Without the action potential generated at the sarcolemma muscle contraction cannot occur.
275
What are the symptoms of malignant hyperthermia?
Symptoms of malignant hyperthermia include muscle rigidity high fever and rapid heart rate.
276
What severe complications can arise from malignant hyperthermia?
Complications in severe cases of malignant hyperthermia may include rapid breakdown of skeletal muscle (rhabdomyolysis) and a high plasma potassium level due to the release of large amounts of potassium from damaged muscle cells.
277
What is the first-line treatment for malignant hyperthermia?
The initial treatment for malignant hyperthermia generally involves rapid cooling of the patient and the administration of dantrolene.
278
What is the mechanism of action of dantrolene in treating malignant hyperthermia?
Dantrolene acts by antagonizing ryanodine receptors which inhibits calcium ion release from the sarcoplasmic reticulum thereby reducing muscle contraction.
279
What are 'calcium sparks' in relation to muscle contraction?
Calcium sparks refer to localized releases of calcium ions from the sarcoplasmic reticulum that play a crucial role in initiating muscle contraction.
280
What is the role of nicotinic acetylcholine receptors at the single-channel level?
Nicotinic acetylcholine receptors facilitate the neuromuscular transmission which is essential for muscle contraction upon receptor activation.
281
What condition is characterized by muscle weakness and is commonly treated with immunotherapy?
Myasthenia gravis is characterized by muscle weakness and can be treated with immunotherapy in the era of biologics.
282
What is rhabdomyolysis and how is it related to malignant hyperthermia?
Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue which can occur in severe cases of malignant hyperthermia due to excessive muscle contraction and cell damage.
283
Which authors contributed to the research on nicotinic acetylcholine receptors published in 2018?
Bouzat C and Sine SM contributed to the research on nicotinic acetylcholine receptors at the single-channel level published in 2018.
284
What publication discusses the immunotherapy for myasthenia gravis in 2019?
The paper by Dalakas MC discusses immunotherapy in myasthenia gravis in the era of biologics published in 2019.
285
What does a high plasma potassium level indicate in cases of muscle damage?
A high plasma potassium level indicates the release of large amounts of potassium from damaged muscle cells which can occur in conditions like malignant hyperthermia.
286
What are the physiological effects of calcium ion release from the sarcoplasmic reticulum in muscle cells?
Calcium ion release from the sarcoplasmic reticulum triggers muscle contraction by interacting with the contractile proteins in muscle fibers.
287
What are congenital myopathies and their association with excitation-contraction coupling?
Congenital myopathies are a group of muscle diseases characterized by poor muscle tone and weakness and are often associated with abnormalities in excitation-contraction coupling which is the process whereby an electrical signal leads to muscle contraction. Research indicates that defects in this process can result in insufficient muscle contraction and overall impaired muscle function.
288
What is the role of ryanodine receptors in muscle function?
Ryanodine receptors are essential for calcium release from the sarcoplasmic reticulum during muscle contraction. They function as calcium channels that are activated by depolarization of the muscle membrane. When activated they release calcium ions into the cytoplasm promoting interaction with myofilaments which leads to muscle contraction.
289
Describe the significance of SERCA pumps in muscle thermogenesis and metabolism.
SERCA (Sarcoplasmic reticulum calcium ATPase) pumps are crucial for muscle relaxation and calcium homeostasis. They transport calcium ions back into the sarcoplasmic reticulum after muscle contraction which is essential for muscle thermogenesis and metabolic regulation. An efficient SERCA pump function ensures proper calcium dynamics influencing muscle metabolism and heat production.
290
How does synaptic control affect motoneuronal excitability?
Synaptic control of motoneuronal excitability involves various neurotransmitters and modulators that can either enhance or inhibit motoneuron firing. This excitability is critical for coordinating muscle contractions and movements and it is adjusted through complex interactions with inhibitory and excitatory inputs.
291
What are the implications of calcium entry in skeletal muscle for muscle physiology?
Calcium entry in skeletal muscle is fundamental for initiating the process of muscle contraction. The influx of calcium ions activates various contractile proteins facilitating contraction. An understanding of this mechanism is crucial for studying muscle physiology and addressing conditions related to muscle dysfunction.
292
What is myasthenia gravis and its pathological mechanism involving antibodies?
Myasthenia gravis is an autoimmune disorder characterized by weakness and rapid fatigue of voluntary muscles. It is caused by antibodies that target and disrupt the function of acetylcholine receptors at the neuromuscular junction leading to impaired neuromuscular transmission and muscle weakness.
293
How do end-plate contributions influence the safety factor for neuromuscular transmission?
The safety factor for neuromuscular transmission refers to the reliability of communication between motor neurons and muscle fibers. End-plate contributions including neurotransmitter release and receptor sensitivity enhance this safety factor by ensuring sufficient post-synaptic depolarization to activate muscle contraction.
294
What are the structural features of the end-plate acetylcholine receptor and its impact on pharmacology and disease?
The end-plate acetylcholine receptor is a pentameric protein complex situated at the neuromuscular junction that binds acetylcholine triggering muscle contraction. Its structure affects pharmacological responses to drugs (e.g. antagonists or agonists) and plays a critical role in diseases such as myasthenia gravis where misfolding or antibody binding can disrupt function.
295
What are the main findings regarding muscle thermogenesis from the research by Periasamy et al. (2017)?
Periasamy et al. highlighted the importance of SERCA pumps in muscle thermogenesis showing that efficient regulation of calcium flux by SERCA is vital for both energy metabolism and heat production in muscle tissues with implications for understanding muscle physiology and disorders.
296
Summarize the structural basis of ryanodine receptor ion channel function according to Meissner (2017).
Meissner (2017) describes how the ryanodine receptor's structure allows it to act as a calcium channel that once activated undergoes conformational changes to open and release calcium ions from the sarcoplasmic reticulum. This process is pivotal in dictating muscle contraction and relaxation dynamics.
297
What is a neuromuscular junction (NMJ)?
The neuromuscular junction (NMJ) is a chemical synapse formed between the motor neuron and muscle fiber which facilitates the transmission of the nerve impulse to cause muscle contraction.
298
What are the key components involved in NMJ development?
Key components include motor neurons muscle fibers (skeletal muscle) synaptic basal lamina and electrical activity which triggers the formation and maturation of NMJs.
299
Which molecules play crucial roles in NMJ development?
Key molecules include acetylcholine (ACh) ACh receptors (AChRs) agrin MuSK (muscle-specific kinase) and LRP4 (low-density lipoprotein receptor-related protein 4).
300
What is the significance of agrin in NMJ formation?
Agrin is a protein that is released by motor neurons which helps to cluster ACh receptors at the postsynaptic membrane of muscle fibers playing a pivotal role in the maturation of the neuromuscular junction.
301
How does muscle activity influence NMJ stability?
Muscle activity promotes NMJ stability and maintenance by regulating the expression of synaptic proteins and ACh receptors and influencing the interaction between the muscle and nerve terminals.
302
What are some mechanisms leading to muscle wasting?
Mechanisms include increased protein catabolism decreased protein synthesis inflammatory cytokine activity mitochondrial dysfunction and hormonal changes.
303
What is myasthenia gravis?
Myasthenia gravis is an autoimmune neuromuscular disorder characterized by weakness and rapid fatigue of voluntary muscles caused by autoantibodies targeting ACh receptors at the NMJ.
304
What are the pathophysiological features of myasthenia gravis?
Myasthenia gravis involves the impairment of neuromuscular transmission reduction of available ACh receptors and the presence of autoantibodies that disrupt normal receptor function.
305
What is the typical onset age of myasthenia gravis and which populations are most affected?
Myasthenia gravis can onset at any age but it most commonly affects women under 40 and men over 60.
306
What are common clinical symptoms of myasthenia gravis?
Symptoms include muscle weakness that worsens with activity ptosis (drooping eyelids) diplopia (double vision) dysphagia (difficulty swallowing) and generalized weakness.
307
What are potential treatments for myasthenia gravis?
Treatments include acetylcholinesterase inhibitors (like pyridostigmine) immunosuppressive drugs (like corticosteroids) and surgical options like thymectomy.
308
How do corticosteroids help in treating myasthenia gravis?
Corticosteroids reduce the immune response by suppressing the production of autoantibodies thereby improving muscle strength and function.
309
Explain the role of LRP4 in NMJ formation.
LRP4 is a receptor that interacts with agrin and MuSK at the NMJ which is essential for synaptic differentiation and function.
310
What is the effect of inflammatory cytokines on muscle wasting?
Inflammatory cytokines can stimulate catabolic pathways in muscle tissue resulting in increased protein degradation and decreased muscle mass.
311
List some other diseases associated with muscle wasting.
Diseases associated with muscle wasting include cancer cachexia chronic obstructive pulmonary disease (COPD) chronic kidney disease and neuromuscular disorders.
312
What are some physiological effects of muscle wasting on the body?
Physiological effects include reduced strength and endurance impaired mobility risk of falls respiratory weakness and negatively affected metabolic health.
