2nd LE Module 6, 7, 8 Flashcards
How does electrical excitation work for neurons?
They use the electrical current to rapidly transmit nerve impulses or action potential
How do muscle cells use electrical excitation?
They use it to initiate muscle contraction
What are the parts of the neuron or nerve cell?
Nerve cell body
Dendrites
Axon hillock
Axon
Node of ranvier
Schwann cells
What is the function of the nerve cell body?
To receive stimulus from dendrites
To send stimulus through nerve axon
True or false.
Nerve cell bodies receive stimulus from the nerve axon and send stimulus through the dendrite.
False
Nerve cell bodies receive from the dendrite and send stimulus through the axon
What are dendrites?
Short processes in neurons
Receive, conduct stimulus and produce voltage changes in response to stimulus
Assist in generating nerve impulses
If a neuron did not have dendrites. Would pain signals still be transmitted? Why?
No. Dendrites are how the nerve cell body receives stimulus. Without it then there would be no action potential sent to muscle cells to retract from pain.
What is an axon hillock?
It processes voltage changes from the cell body and dendrites
Assists in generating nerve impulse
What is an axon?
A singular, long process in neurons
Conducts nerve impulses to the axon terminal or neuromuscular junction
What is a neuromuscular junction?
The juntion between nerves and muscles. Muscles receive electrical stimulus through this that allows them to contract.
What is the Node of Ranvier?
Gaps between the myelin sheaths in the nerve axon
Facilitates generation and transmission of nerve impulses
What are Schwann cells?
Cells that generate myelin sheaths
Myelin sheaths increase the transmission speed of signals
How do Nodes of Ranvier facilitate generation and transmission of nerve impulses?
Through the opening of sodium channels that are present at every Node of Ranvier.
What is the distribution of ion channels in myelinated neurons?
Surface of myelin in nerve axons = <25
Axon terminal = 20-75
Initial segment of axon = 350-500
Nerve cell body = 50-75
Nodes of Ranvier = 2000-12000
What is resting membrane potential (RMP)
Difference between inside & outside of all cells
Determine by measuring the voltage of ICF vs ECF
What are the RMP of neurons, muscle cells, thyroid cells, and fat cells?
Neurons = -70 mV
Muscle cells = -70 mV
Thyroid cells = -50 mV
Fat cells = -40 mV
In general, what causes the negative RMP of the ICF vs the ECF?
Due to the unequal flow of ions across the membrane
Why is the interior of the cell slightly negative?
Due to ion concentration difference
Cell membrane’s selective permeability
Movement of ions across the membrane
What specific ions cause negative potential of ICF?
K and Negative Charge Protein (NCP)
What causes the potential difference in ECF?
High concentration of Na and Cl ions
True or false.
The negative change of ECF is due to NCP which remains inside the cell because it is too large to pass through the membrane.
False.
The negatve change of ICF is due to the NCP
True or false.
While at rest, Na ion conductance is 10x higher than K ion conductance.
False.
K ion ion conductance is 10x higher than Na ion because the cell membrane is highly permeable to K ions.
What are the two factors that determine the RMP?
concentration gradient for ion (chemical gradient)
membrane permeability or ion conductance (electrical gradient)
Situational question.
If K+ is abundant in the ICF what happens to the cell?
It will cause K+ to drive out of the cell and follow its concentration gradient by leaking out
Situational question.
If Na+ is abundant in the ECF what happens to the cell?
Na will follow its concentration gradient and move into the cell
What is the cell membrane permeability for Na ions?
Not very permeable
The Na+ ions leak into the cells via leaky channels but are pumped out by the Na-K pump at the same rate it leaks in
What is the cell membrane permeability for K ions?
Highly permeable to K+ ion and leaks out of the cell
Cell actively pumps K+ back into the cell but leaks at the same rate
True or false.
The chemical gradient and electrical gradient contribute to the net movement of negatively charged ions out of the cells.
False.
Chemical and electrical gradients equate to net movement of positively charged ions out of the cell
What causes cells to have an RMP?
Na-K ATPases pumping out 3Na in the cell and 2K out of the cell.
K+ leaving the cell through leaky K+ channels
Free phosphates and proteins that dissociate from K+ remaining in the cell
True or false.
K+’s chemical gradient pushes it out of the cell.
True. Because K+ is more abundant in the ICF thus leaky channels naturally push it down its concentration gradient out of the cell into the ECF.
What are the determinants of resistance across the cell membrane?
- Number of ion channels
- Type of ion channels
True or False.
Both the chemical and electrical gradients drive K+ out of the cell.
False.
Only the chemical gradient drives K+ out of the cell.
Electrical gradient opposes the chemical gradient since the + charge of K is attracted to the negatively charged proteins (NCP) in cell
What drives Na+ into the cell?
Both chemical and electrical gradient. Since Na+ is attracted to the negative interior of the cell.
What does the Nernst Potential measure?
The amount of work that can be done by an ion diffusing down its gradient
What is the unit of Nernst Potential?
electrical equivalent Veq or mV
When there is no net movement of K+, what is the Nernst Potential of K+ and Na+
K+ = -90mV (90%)
Na+ = +70mV (10%)
RMP EK+ + ENa+ = -70mV
What is a current?
It is the flow of ions across the cell membrane and eliminates electrical potential (kinetic movement?)
What is the function of the cell membrane in regards to the current?
It acts as a resistor by resisting the flow of ions down their concentration gradient
What happens if the resistance is high?
The current will be low and the cell membrane channels will be closed thus not allowing the flow of ions
What happens if resistance is low?
Current will be high and the cell membrane channels will be high and allow the flow of ions
True or False.
Recall the conductance-time graph of K+ and Na+ channels. Both Na and K channels have the same maximum conductance.
True
True or False.
Na+ and K+ channels have the same activation and inactivation time.
False.
Sodium channels have an earlier activation time and are open briefly before slowly closing.
K+ channels have a slower activation time but an immediate inactivation time.
What happens when cells are electrically stimulated?
They generate action potential or nerve impulse
What are the requirements for generating an action potential?
- Part of a neuron to stimulate
- Change in membrane potential
- Electrical stimulus is strong enough to cause depolarization
- Change in membrane conductance
What part of the neuron is stimulated to generate an action potential?
Membrane of axon
Change in membrane potential must be from __ mV to __ mV
-70 mV to +45 mV
During depolarization what is the overall potential of the membrane?
Less negative
Why is there a need to have a strong stimulus for depolarization?
In order to open the voltage gated Na channels
What causes changes in membrane conductance
An increase in membrane conductance of Na and K ions
When doesnt an action potential occur?
Subthreshold stimulus
What is the principle that explains the mechanism of AP generation in regards to stimulus?
All-or-none principle or quantal response
What happens if the electrical stimulus reaches the threshold potential?
Action potential occurs
What happens if a suprathreshold stimulus occurs?
Action potential occurs
True or False.
The size and form of the AP generated by a suprathreshold stimulus is different from the AP generated by a threshold stimulus.
False.
The AP size and form remain the same
What happens if a subthreshold stimulus occurs?
AP is not generated.
What happens after proper nerve stimulation?
An action potential or nerve impulse
What does the all or none process of action potential mean?
It means its a domino effect where AP is conducted through the entire length of nerve axons without diminishment
Basically its either the first section starts an action potential and cascades to other parts of the membrane or nothing happens at all.
The formation of AP or nerve impulses stimulates the generation of new AP or nerve impulses in the next section of the nerve axon membrane
Why are nerve impulses so important?
They are the primary signal used by the nervous system
Nerve impulses are used to regulate physiologic activities of animals such as?
- Stimulate other neurons and other cells
- Stimulate release of neurotransmitters
- Regulate sensory functions
- Regulate motor functions
- Regulate glandular secretions
What are the 6 phases of action potential?
- Threshold potential (Resting)
- Depolarization or up stroke
- Overshoot
- Repolarization or down stroke
- After depolarization
- Hyperpolarization
What happens during the threshold potential step or RMP step?
The Na+ channel activation gate or M gate is closed
What happens during depolarization?
Na+ channel activation gate or M gate opens
What causes Na+ channels to open and increase the membrane potential?
A nerve stimulus
What happens if the stimulus is unable to reach the threshold?
Depolarization does not occur as not enough Na+ ions entered into the cell to reach the threshold potential
What is the threshold potential in mV?
-55 mV
What happens during the overshoot step?
Na+ channel becomes refractory
Activation gate closes
Inactivation gate (H gate) opens
What does it mean for a Na+ channel to be refractory?
It means that no more Na+ ions can enter into the cell
What happens during repolarization?
K+ channel activation gate opens
Resetting of Na+ channel activation and inactivation gates
What are the properties of the K+ channel?
It is regulated by one gate (N gate)
The Activation (N) gate covers the extracellular side of the K+ channel
The opening of the N gate (activation of K+ channels) allows K+ ions to flow through the K+ channel
Absence of inactivation gate in K+ channel
What causes the resetting of Na+ channel activation and inactivation gates?
It is caused by K+ leaving the cell and the two gates reset to their original positions
Can a neuron be refractory to stimulation? If yes, explain how.
Yes
Neurons have a refractory period from the beginning of 1 action potential to the time the RMP is restored
They have two refractory periods, one of which is an absolute refractory period where no stimuli AT ALL can trigger action potential.
What are the two phases of refractory period?
Absolute and relative refractory period
What happens during the absolute refractory period?
No stimulus is able to excite the nerve and it occurs from the time the action potential is fired until 3/4 of repolarization
Can any stimulus trigger AP during the relative refractory period?
No, only stronger than normal stimuli can excite the nerve
Where does the action potential propagate?
It propagates along the nerve axon
Outline the pathway of the generation and propagation of an action potential?
In the presynaptic neuron cell body resting potential receives a stimulus
This gives way to a graded potential in the axon hillock which produces action potential
The action potential propagates along the nerve axon
The AP triggers synaptic activity in the postsyaptic cell
Which triggers information processing
True or False.
The entirety of the nerve axon is excited at the same time when AP is conducted.
False.
It is a series of depolarization, repolarization, and resting.
The soma end of the axon first becomes depolarized, which spreads down the axon.
As the AP spreads, previous sections will repolarize and eventually enters the resting phase.
What is the difference between an unmyelinated and myelinated axon?
Presence of myelin sheaths produced by the Schwann cells.
Unemyelinated axons are small and thin while myelinated axons are large and thick
Unmyelinated axons are slow propagators of AP while myelinated are rapid propagators
Where does the AP propagate from in unmyelinated axons vs myelinated axons?
In unmyelinated axons, AP is propagated from the cell body or dendrites
In myelinated axons, AP is propagated from the nodes of Ranvier
Where are myelinated axons normally found?
Axons of major descending and ascending nerves of the spinal cord
Sensory axons for tactile discrimination
All motor neurons
Where are unmyelinated axons commonly found?
In nerves that innervate muscles that require constant contraction such as those for posture like our back
What are the types of propagation or conduction of nerve impulses?
Continuous
Saltatory
Orthodromic
Antidromic
What is a continuous AP?
An action potential that originates from one point of the neuron membrane and depolarizes adjacent areas of the membrane so that APs continue to form along the membrane
What is a saltatory AP?
An AP that jumps from 1 node of ranvier to another and requires less energy
Which is faster, a continuous or saltatory AP?
Saltatory
What is an orthodromic AP?
AP that is propagated towards the nerve axon terminal
What is an antidromic AP?
AP is propagated in opposite directions
True or False.
Smaller nerve diameters have a high surface area thus allowing faster conduction of APs.
False.
The larger the diameter of the nerve, the faster the fibers conduct AP
What are the three types of Nerve fibers?
Type A
Type B
Type C
What are the features of the Type A fibers?
Large myelinated nerve fibers for proprioception, somatic motor touch, pressure, motor to muscle spindles, pain, touch, and cold
There are 4 kinds of Type A fibers. What are they?
Alpha
Beta
Gamma
Theta
True or false.
The following Type A fibers are arranged in ascending order of diameter and conduction velocity.
Theta - Gamma - Beta - Alpha
True.
Alpha Type A fibers are the largest in diameter and have the fastest conduction velocity.
Beta Type A fibers are the 2nd largest and 2nd fastest
Gamma and Theta Type A fibers are thin and not as fast
What are t he features of Type B nerve fibers?
Small myelinated nerve fibers, for the preganglionic autonomic
What are the features of the Type C fibers?
Unmyelinated nerve fibers and are found in the dorsal root of the spinal cord - responsible for pain and temperature sensing, reflexes, and mechanoreception.
What is myelination?
The formation of the myelin sheath surrounding the nerve axon or fiber
Why is a myelin sheath important?
It allows for the faster conduction of nerve impulses or action potentials
What produces the myelin sheath?
Schwann Cells in the Peripheral Nervous System
Oligodendrocytes in the Central Nervous System
When does myelination begin?
During fetal development and rapidly after birth
What is myelin made out of?
Lipids
Specifically Cerebroside, Cholesterol, Lecithin, Sphingomyelin
Why is the myelin sheath important in the nervous system?
Because they make excellent electrical conductors with the AP sliding right over or through the lipid sheath and skipping large sections of the axon by only triggering AP at the nodes of Ranvier
What are oligodendrocytes?
It produces myelin for CNS
Sends off many processes to form myelin on many axons
No repair of axons after damage
It has fewer Nodes of Ranvier
What is hypomyelination?
Impediment in the formation of normal myelin
What is dysmyelination?
Genetic disorder in myelinogenesis which leads to the formation of abnormal myelin
What are the two kinds of demyelination?
Primary and secondary demyelination
What is primary demyelination?
It is the early destruction of myelin with relative sparing of axons
What is secondary demyelination?
Damage in myelin as a result of damage to neurons (axons)
What is canine degenerative myelopathy?
An autoimmune disease that causes the destruction of the myelin sheath in the CNS
What breeds have a predilection to canine degenerative myelopathy?
German Shepherds
Welsh Corgis
Siberian Huskies
Labrador Retrievers
What are clinical signs for Canine Degenerative Myelopathy?
Lack of coordination in hind limbs
Weakness in hind limbs
Dog can no longer walk
Knuckle over
Crossing or dragging of feet
Notice how most of the clinical signs are related to the limbs.
What nerve fibers are targeted by Degenerative Myelopathy?
Nerve fibers that transmit motor signals from the brain to the limbs and those that transmit sensory signals from the limbs to the brain
What is CNS Demyelination?
It is an inherited disease which interferes with the functional maturation of oligodendrocytes.
What is the cause of CNS Demyelination?
Gene mutation or in utero exposure to Trichlorfon
What kind of animals can obtain CNS Demyelination?
Pigs
Cattle
Sheep
Siamese Kittens
Dogs
What dog breeds are predilected to CNS Demyelination?
Chowchow
Springer Spaniel
Dalmatian
Samoyed
Lurcher
Bernese Mountain Dog
Vizsla
Weimaraner
Australian Silky Terrier
True or False.
Clinical signs of CNS Demyelination begin at 10-12 days old or weaning age
True
What are the clinical signs of CNS Demyelination?
Whole body tremors
Difficulty in standing, ambulation
Pendular nystagmus or jerky nystagmus
What does whole body tremor look like?
Limbs, trunk, head, eyes are awake and excited with tremors increasing and reappearing
What does Difficulty in standing or ambulation look like?
Weakness of hind limbs
What does pendular or jerky nystagmus look like?
When eyes are involuntarily moved
When can we observe deficient postural reactions?
10-12 days old or weaning age
What is PNS Demyelination?
An inherited disease which interferes with the functional maturation of Schwann cells
What is the cause of PNS Demyelination?
Gene mutation
Which breed has a predilection to PNS Demyelination?
Golden retrievers
Which sex has a predilection to PNS Demyelination?
Male
What are the symptoms of PNS Demyelination?
Ataxia
HL Paresis
Muscle Atrophy
Hyporeflexia to areflexia
Absence of tremors
When can we observe symptoms?
5-7 weeks of age
What is the cause of CNS demyelination in Weinmareners
Genetic mutation in CNS myelination
Delay in CNS myelination
When can we observe CNS Demyelination in Weinmareners?
12 to 14 days old in pups
What are t he clinical signs of CNS demyelination in Weinmareners?
Sever tremor
Loss of coordination
True or False.
CNS demyelination in Weinmareners disappear by 1 year.
False.
Most cases disappear by 3-4 months
Others persist for life but tremors are mild
What is a synapse?
A specialized junction that transfers nerve impulse from a presynaptic neuron (N1) to a postsynaptic neuron (N2) with the release of neurotransmitters in the synaptic cleft
What are the types of synapse?
Axo-axonic
Axo-dendritic
Axo-somal
Dendro-dendritic
Dendro-somatic
What happens after an action potential conducts along a nerve axon and terminates at a synapse?
It causes the release of a neurotransmitter in the synaptic cleft
What is the effect of neurotransmitters being released from the synaptic cleft?
The neurotransmitters can bind to receptors in the postsynaptic neuron to cause an effect like opening of ligand gated channels
The release of neurotransmitters can cause 4 responses in regards to cell membrane and its potential. What are these four?
Fast EPSP = excitatory depolarization
IPSP = inhibitory hyperpolarization
Slow EPSP = excitatory depolarization
Coordinated intracellular response
What are the outcomes of a rapid, short-acting fast synaptic potential?
Binding of NTs to chemically gated ion channel
Opens ion channels
Can cause more Na+ to go in and cause EPSP
Can cause more K+ out or Cl- in and cause IPSP
What are the outcomes of a slow synaptic potential and long term effects?
Binding to a G-protein coupled receptor
Activation of a second messenger pathway
Alteration of open state of ion channels causing ion channels to close
Less Na+ In which causes IPSP
Less K+ out which causes EPSP
Or the modification of existing proteins or regulates new synthesis of proteins causing a coordinated intracellular response
What are the kinds of neurotransmitters released during a synapse?
Acetylcholine
Dopamine
GABA
Glutamate
NE, E
Enkephalins, Endorphins
What are Acetylcholines for?
For wakefulness, attentiveness, anger, aggression, other effects, listed in physiology of nervous system
What is dopamine for?
Controls movement,, posture, modulates mood, for positive reinforcement and dependency
What is GABA for?
Involved in regulating motor control, vision, anxiety
What is glutamate?
Involved in memory, learning
What is norepinephrine and epinephrine for?
Stress, regulates food intake
What are enkephalins and endorphins for?
Control of pain and euphoric feeling
What are types of synapses based on the number of presynaptic or postsynaptic neurons?
Convergent synapse
Divergent synapse
What is a convergent synapse?
A junction that receives from different neurons (convergence, multiple) or from a single neuron with multiple axons (convergence, single)
True or false.
The ratio of presynaptic neurons to postsynaptic neurons in a convergent synapse is from 0.5 to 1.
False
Ratio of presynaptic neurons to postsynaptic neurons is greater than 1
What kind of summation do convergent synapses cause?
Spatial summation
What is a divergent synapse?
A junction that has two or more postsynaptic neurons in the same pathway or multiple pathways.
What is the ratio of presynaptic neurons to postsynaptic neurons in a divergent synapse?
Less than 1
What kind of summation are divergent synapses responsible for?
Temporal Summation
What is an excitatory post synaptic potential (EPSP)?
Positive postsynaptic potential that promote the generation of nerve impulses
What is an inhibitory post synaptic potential (IPSP)?
Negative postsynaptic potential that prevents the generation of nerve impulses
Which of the post synaptic potential causes depolarization?
EPSP because it makes the cell more positive
Which of the post synaptic potentials cause hyperpoolarization?
IPSP because it makes the already negatively charged cell negative
What is presynaptic inhibition?
It is the firing of an inhibitory neuron that blocks the release of a neurotransmitter at one synapse
Only one of the target cells will be blocked
What is postsynaptic inhibition?
It is the simultaneous firing of one excitatory and inhibitory neuron.
This results in a signal below the threshold potential so no action potential is generated and no response occurs in the target cells
All targets are blocked equally
What is a temporal summation?
It is the transmission of nerve impulses at a slow or rapid frequency at succession over the cell
What is spatial summation?
The transmission of nerve impulses simultaneously to the same cell from varying numbers of nerve fibers to the same neuron
What 3 classes of substances can affect nerve impulse transmission?
Nerve poison or neurotoxins
Local anesthetics
General anesthetics
What neurotoxins are used?
Scorpion venom
What is the mechanism of action for neurotoxins?
It opens Na+ channels but shuts K+ channels and disrupts AP
What is an example of local anesthetics?
Novocaine and xylocaine
What is the mechanism of action for local anesthetics?
It blocks Na+ channels and blocks AP sensory neurons for pain recognition
What are examples of general anesthetics?
Ether
Chloroform
What is t he mechanism of action of general anesthetics?
It prolongs the opening of Na channels and prevents the propagation of AP
How is RMP and Action Potential recorded?
Intracellular recording - patch clamp
Extracellular recording
How does intracellular recording-patch clamp work?
It records the change in membrane potential in a cell or isolated patch of cell membrane
It monitors the opening and closing of ion channels
What is extracellular recording?
It is used to evaluate and monitor electrical activity of specific tissues or glands in the body of animals?
What are examples of extracellular recording?
ECG - heart
Electroencephalography - brain
Electromyography - muscles
Brainstem Auditory Evoked Response (BAER) - hearing
What are the three types of muscles?
Skeletal
Smooth
Cardiac
Which of the muscles have cross striations?
Both skeletal and cardiac
Which of the muscles are involved in involuntary contraction?
Smooth and cardiac
Outline the overall anatomy off skeletal muscles.
Epimysium -> Muscle Fascicles
Muscle fascicles -> Perimysium -> Endomysium
Endomysium -> Muscle fibers
Muscle fiber -> Sarcolemma
What is a sarcolemma?
It is the membrane of the muscle cells
What are myofibrils?
Threadlike strands within a muscle fiber and make up sarcomeres which are separated by Z disk
What are our contractile filaments?
Thin (Actin, Troponin, Tropomyosin) Filaments
Thick (Myosin) Filaments
Where are our transverse tubules located?
At the junction of the A (thick filaments) and I (thin filaments) band
What is the sarcoplasmic reticulum?
It forms contacts with the transverse tubules and is the storage site of Ca ions
What is a z-line or disc?
It marks the boundaries of the sarcomere and anchors the thin filaments
It transmits tension from one sarcomere to the next during a muscle contraction
What makes up our sarcomere?
The I band and A band
What makes up our thin filaments?
Actin
Tropomyosin
Troponin Complex
What makes up our thick filaments?
Myosin
What is actin?
A type of thin filament made out of 2 chains and is important for muscle contraction
It is composed out of multiple G and F actin proteins
What is tropomyosin?
A type of thin filament that coils around actin and covers the myosin binding site
What is troponin?
A type of thin filament that contains Ca binding sites and controls the position of tropomyosin
Made out of Troponin T, I, and C
What are thick filaments?
A type of filament that is composed of 300 myosin molecules
They are interspersed between thin filaments at the center of the sarcomere
What are the sarcomere supportive proteins?
Nebulin
Tropomodulin
Titin
What is the function of Nebulin?
It defines the length of the thin filaments
What is the function of Tropomodulin?
It caps the end of the thin filaments
What is the function of Titin?
It enters the thick filament and is shaped like a spring coil
What do the sarcomere banding patterns represent?
The interdigitating or intercalating light and dark bands
What is a dark or Anisotropic (A) band?
It contains the thick filaments
What is a light or Isotropic (I) band?
It contains the thin filaments and the Z disc
What is the H band or H zone?
The area of A band that lacks the thin filaments
It is also the area that is covered by thin filaments during a contraction
What is the M line?
A line at the center of the H band
It is a region of thick filaments and lacks a cross band
The Transverse Tubules and Sarcoplasmic Reticulum form what?
A TRIAD Arrangement
True or False.
The sarcolemma has invaginations which extend as the transverse tubules and are attached directly to the sarcoplasmic reticulum to form the TRIAD arrangement.
False.
The transverse tubules are attached to the terminal cisternae which become the sarcoplasmic reticulum
What is a neuromuscular junction or motor end plate?
It is the site of synapse and connects the neurons to the muscles and serves as a way for muscles to receive signals from the nervous system
What is the neurotransmitter released by the neuromuscular junction?
Acetylcholine
What is the function of Acetylcholine in the NMJ?
Causes an action potential that depolarizes the skeletal muscle fiber
Why is it important that acetylcholine depolarizes the skeletal muscle fiber?
So that it opens voltage gated Na+ channels which in turn allow voltage gated Ca2+ channels to open the gated Ca2+ release channels and release Ca2+ from the sarcoplasmic reticulum and allow for contraction of muscle fibers
True or False.
The action potential from the neuromuscular junction allows for the release of Ca ions from the sarcoplasmic reticulum.
True.
The action potential spreads to the T-tubule membrane which have intrinsic voltage-sensitive proteins which are bound to Ca2+ release channels in the sarcoplasmic reticulum membrane. The action potential then allows for the opening of these Ca2+ release channels and frees Ca ions from the lumen of the sarcoplasmic reticulum into the cytosol of the muscle cell
Why is calcium so important in muscles?
Because it exposes the binding sites for myosin in the actin (thin) filament and allows for muscle contraction
The contraction of skeletal muscles is primarily due to what?
The crossbridging of actin and myosin
Outline the steps of skeletal muscle contraction and relaxation
- ATP binds to the myosin head
- The ATP allows the myosin head to bind to the thin filament
- The power stroke of the thin filament pulls back the myosin head and locks it in place and releases ATP (this is the contraction)
- New ATP binds to the myosin head which releases the myosin from the thin filament
- ATP is hydrolyzed which causes t he myosin to return to its original orientation
What is the sliding filament theory?
It is a model of muscle contraction. The actin and myosin filaments in a sarcomere slide past one another without shortening
What are the types of skeletal muscle contraction?
Muscle twitch
Staircase
Incomplete tetany
Complete tetany
Summation
Fatigue
How does a muscle twitch appear as in a graph?
It is bell-shaped with a period of contraction and relaxation
How does a staircase contraction appear in a graph?
Increasing amplitude of contraction
How does incomplete tetany appear in a graph?
Fusing contraction due to frequent stimulation of muscle prior to relaxation
How does complete tetany appear in a graph?
Fused contraction (high amplitude with no signs of relaxation) due to rapid stimulation of muscle
How does summation appear in a graph?
The amplitude of the 2nd contraction is higher than the 1st contraction due to stimulation of muscle prior to relaxation
How does fatigue appear in a graph?
Prolonged muscle contraction since it is the inability of contractile filaments and metabolic processes of muscle to supply the same work output
What compound is needed for muscle contraction?
ATP
What is the protein that breaks down ATP during a skeletal muscle contraction?
myosin ATPase
What are the sources of ATP for a skeletal muscle contraction?
Phosphocreatine (PC)
Glycolysis
Oxidative phosphorylation
Which ATP source is the largest contributor of ATP for skeletal muscle contraction?
Oxidative phosphorylation because it lasts as long as O2 is in the body
What muscles use Oxidative phosphorylation the most?
Those that are always contracted such as the muscles of posture like the epaxial mm.
What are the biochemical properties of skeletal muscle fibers?
Oxidative capacity
Type of ATPase
What are the contractile properties of skeletal muscle fibers?
Maximal force production
Speed of contraction
Muscle fiber efficiency
There are two types of fibers. What are they?
Slow fibers (postural mm.) or Type I fibers
Fast fibers or Type II fibers
What are the two kinds of Type II fibers?
Type IIa and Type IIb
What is the metabolic property of Type I fibers?
Oxidative phosphorylation
What type of motor neuron is used by slow fibers?
a1 unmyelinated
Which muscle fiber has the smallest neuron size?
Slow fibers
What is the conduction speed of Type I fibers?
Slow
Why do slow fibers have slow conduction velocity?
Because they are unmyelinated
The recruitment threshold of Type I fibers is low. Explain why.
Because the motor neuron is small and the muscles it innervates need to constantly contract to maintain stability thus it has a lower threshold for a contraction
What are the differences between Type IIa and Type IIb fibers?
Type IIa fibers use oxidative phosphorylation while Type IIb fibers use glycolysis
Type IIb fibers are also faster in conducting APs than Type IIa
Correlate the type of motor neuron of the fast fibers with their conduction velocity.
The fast fibers have intermediate to fast speed which is aided by the a2a and a2b myelinated motor neurons
Why do both fast fibers have high recruitment thresholds?
Because they have large motor neurons which require larger stimuli
What other characteristics do our slow fibers have given what we know about their biochemical and conductive properties?
They are unfatigueable
They have a lot of mitochondria due to relying on oxidative phosphorylation
They are vascular or have a large capillary supply and very red so that they have a lot of O2
Between the two Fast fibers, which one is more fatigable?
Type IIb
They are fatigable because they rely more on glycolysis and phosphocreatine and though they contain a lot of glycolytic enzymes they are faster and do not last long
Knowing that Type IIb fibers rely on glycolysis and PC while Type IIa relies on oxidative phosphorylation and glycolysis, how would one discern between the two through observation of the muscles only?
By observing their colors.
Type IIb fibers have fewer mitochondria and a low concentration of myoglobin since they don’t rely on oxidative phosphorylation so they have a white appearance.
In descending order, rank the 3 fibers based on their maximal shortening velocities?
Type IIb
Type IIa
Type I
Fast twitch or Type IIb muscles have a maximum contraction of 3-5 milliseconds. What muscle would make use of this?
Eyeball muscles
Intermediate twitch (Type IIa) muscles have a 10-20 millisecond maximum shortening velocity. What muscles would require such a speed?
Muscles that exhibit most body movements
What muscles would make use of the slow twitch muscles?
Postural muscles
How is force generated in muscles?
By overlapping myosin and actin
AKA the sliding filament mechanism
Why is force important in muscles?
It is necessary for stretching a relaxed muscle
What happens to the muscles when it relaxes?
The distance between the origin and insertion of the muscle increases
What happens when a muscle contracts?
It decreases the distance of a muscle’s origin and insertion around a lever
What are the factors that can increase the force of skeletal muscle contractions?
Recruit or increase the # of active motor units
Increase frequency of stimulation (frequency of summation) of individual motor units
If force increases with more motor units, what kind of work is needed when only small motor units are used?
Fine work
What are the factors involved in the generation of force needed for skeletal muscle contractions?
Length of muscle
Shortening velocity of muscle (rate at which a muscle is shortened)
What factors affect the force that develops when muscles contract?
The initial length of muscle (preload)
Load (force) applied to the muscle before it is stimulated
True or False.
A long relaxed muscle generates more force.
False.
A half-contracted muscle generates more force because it has a higher shortening velocity, still has available binding sites for actin and myosin
Why is maximal force obtained when the preload (initial length of muscle) is set close to their resting length?
Because it allows for most efficient overlap between the actin and myosin filaments
When a muscle contraction is initiated then there are more myosin heads that are readily available to bind with the the actin filaments
What happens if you increase your preload?
There is decreased overlap between thick and thin filaments
When a muscle contraction is initiated then there are less myosin heads binding with actin filaments
What happens if you decrease your preload?
The bumping of actin filaments make it difficult to bind with myosin
There is bumping of thin filaments, binding sites are exhausted and are represented by tetany
True or False.
The heavier the weight a muscle lifts (Afterload), the slower the velocity of muscle shortening
True.
This is because there is an inverse relationship between the force of muscle contraction and the velocity of muscle shortening
What are the classifications of voluntary contractions?
Eccentric contraction
Concentric contraction
What is an eccentric contraction?
It is a contraction where the force generated is not enough to overcome resistance
What happens to the muscle during an eccentric contraction?
The muscle lengthens while it is still contracted and it is used to decelerate body parts
This means that overlap is not fully saturated and there are still actin and myosin heads being released
Give an example of an eccentric contraction?
A bent elbow straightening out and moving away from the shoulder
What is a concentric contraction?
It is a contraction where there is enough force generated to overcome the resistance on the muscle
What happens to the muscle during a concentric concentration?
The muscle shortens as it contracts
Give an example of a concentric contraction?
Bicep curls
Why is ATP so important in muscle contraction?
Because the myosin cross bridge cycle uses ATP
ATP is needed to pump Ca ions into the SER
ATP is needed to activate the Na-K pump to reestablish the membrane potential
What are the two types of smooth muscles?
Single unit smooth muscles or Syncytial smooth muscle
Multi-unit smooth muscle
Where are the smooth muscles found?
Walls of hollow organs (GIT)
Eyes (iris of the eye)
Skin (Arrector pili muscle)
What is the shape of smooth muscles?
Spindle-shaped with nucleus
What is the arrangement of myosin and actin in smooth muscles?
Dispersed throughout the smooth muscle cell cytoplasm
Is there interdigitation between myosin and actin in smooth muscles?
No, there is no distinct sarcomere
What structures are present or developed in skeletal muscles that are absent or not as developed in smooth muscles?
Sarcoplasmic reticulum and Transverse tubules
What does the absence of T-tubules and few SR imply in smooth muscles?
That their Ca2+ source is not in the SR but rather in the ECF
What are dense bodies in smooth muscles?
They are similar to the Z-discs of skeletal and cardiac muscle
They are attached to the sarcolemma and anchors the actin
What are single unit smooth muscles?
Smooth muscle cells joined by gap junctions that synchronize depolarization and allows muscles to contract as a single unit
Where can we find the Single Unit Smooth Muscle?
The walls of GIT, urinary and reproductive system
What is the function of Syncytial muscle?
It permits smooth muscles to stretch during the filling of hollow organs, contract and immediately relaxes
It also maintains smooth muscle tone when organ empties and shrinks
What are multi-unit smooth muscles?
They are smooth muscle cells that do nott possess gap junctions and contractions dont spread from one cell to another
Where can we find the multi-unit smooth muscle cells?
In large blood vessels
Respiratory tract wall
Eyes
What is the function of the multi-unit smooth muscle?
To keep contractions confined to the cell that is stimulated and to contract as a response to stimulus from autonomic nerves or hormones
Whatt controls the smooth muscle contractions?
Neural stimulation by autonomic nervous system
Hormones
Local factors
The autonomic nervous system is divided into two divisions. Parasympathetic and Sympathetic. What are their neurotransmitters released and action?
Acetylcholine : contraction
Epinephrine & Norepinephrine : relaxation
What can stimulate spontaneous action potential in smooth muscles?
Presence of varicosities in the axons
Presence of pacesetter cells in the walls of hollow organs
What do these varicosities contain?
Acetylcholine
What maintains the structure and anchors the smooth muscle cell?
Attachment plaques and dense bodies
What are attachment plaques?
They serve as attachment sites for actin filaments and link the contractile apparatus of the muscle cell to the extracellular matrix
They also aid in transmitting force
Where are attachment plaques located?
Located on the sarcolemma (cell membrane) of smooth muscle cells
What are attachment plaques made of?
Integrin
What are dense bodies?
Serve as anchorage points for actin filaments and are similar to the z-discs
They help coordinate contraction by holding actin filaments in place and maintaining structure of the cell during contraction
Where are dense bodies found?
In the cytoplasm and along the inner surface of the plasma membrane
What are dense bodies made of?
A-actinin
Are attachment plaques the same as dense bodies?
No.
They are different
Attachment plaques are found on the sarcolemma and connect the cell to the ECM
Dense bodies are found in the cell and are involved in anchoring actin filaments
The sarcoplasmic reticulum of smooth muscle cells are only few. Why?
Because smooth muscle cells only use the SR as a minor source of Ca ions
What do you call the invaginations of the SR membrane?
Caveolae
What is the function of the Caveolae?
facilitate ion release from the SR
What is the major source of Ca ions for smooth muscles?
ECF
The smooth muscle myosin head has 4 light chain proteins. What are these?
2 Essential Light chains
2 Regulatory Light chains
They also have two Globular head or main domains
What do the light chain proteins and head domains form in the SM thick filament?
“Side-polar” cross bridge arrangements
There are three kinds of actin in smooth muscles. What are they?
Actin
Tropomyosin
Caldesmon
What is the function of actin filaments in smooth muscle cells
Contain the myosin binding site
What is the function of tropomyosin in smooth muscle cells?
covers the myosin binding sites in actin filaments
What is the function of the caldesmon?
Ca-Calmodulin binding protein
Similar function to troponin in skeletal muscles
Outline the steps of a smooth muscle contraction
- Action potential increases Ca conc in smooth muscle fibers
- The Ca ions bind with calmodulin
- A Ca-calmodulin complex binds with caldesmon and activates the myosin light chain kinase
- Changes in tropomyosin structure to expose the myosin active sites
- Activation of myosin via phosphorylation of the myosin regulated light chain
- Attachment of myosin with actin via cross bridging
- Smooth muscle contraction
What does a smooth muscle contraction look like and why?
Because the dense bodies are within the periphery of the cell and attached to the sarcolemma it pulls the cell inward to itself
How does a smooth muscle relax?
Via an increase in Myosin Light Chain Phosphatase activity and a decrease in Ca ion concentration
What is the action of the Myosin Light Chain Phosphatase (MCLP)
It catalyzes dephosphorylation of the myosin regulated light chain
Where is MCLP found?
In the fluids of smooth muscle cells
What is the effect of the MCLP?
Smooth muscle relaxation via detachment of actin and myosin
True or false.
Smooth muscles and Skeletal muscle both have prolonged tonic contraction that can last for hours or days,
False.
Only smooth muscles exhibit prolonged tonic contraction because the slow cycling of myosin occurs 1\10 in smooth muscles vs 1\300 in skeletal
What are the other explanations for the prolonged smooth muscle tonic contraction?
Slow initiation of smooth muscle contraction in response to Ca ions
Slow onset & prolonged smooth muscle contraction
Latch bridge mechanism
True or false.
Stress relaxation is only in smooth muscles.
True
Why do latch bridges occur in smooth muscles?
Because dephosphorylated myosin remains attached to actin
Why are latch bridges important?
It allows for the long term maintenance of tone in smooth muscle organs with little energy expenditure
What are the organs exhibiting latch bridges?
GIT, urinary bladder, gall bladder, ureter
What is stress-relaxation of smooth muscles?
It is the capacity of smooth muscles to return to its original force of contraction after it has been contracted or stretched
Why is stress relaxation imporant?
It allows a hollow organ to maintain the same amount of pressure inside its lumen despite a long-term, large change in volume
What are some organs that exhibit stress relaxation?
Smooth muscles of hollow organs
- uterus, ureter, urethra, urinary bladder
True or False.
Stress relaxation works in reverse.
True.
Whether or not a change in pressure comes about via an increase or decrease in pressure, the pressure will always revert back to its original level
What are the three kinds of action potential in smooth muscles?
Spike potential
Repetitive spike potential
Action potential with plateau
How long does a spike potential last and what organ exhibits it?
10-50 seconds
GIT
How long does a repetitive spike potential last and what organ exhibits it?
8-10 seconds
GIT
How long does an action potential with plateau last and what organ exhibits it?
0.3 - 0.4 millisecond
Ureter, uterus, vascular smooth muscles
What is the shape of the cardiac muscles?
Ribbon like and extensively branching
What is unique about the cardiac muscles?
It is syncytially connected at their ends by the intercalated discs
What is the function of the intercalated discs?
It allows coordinated contractions of cardiac muscles to pump into the circulatory system
Do cross striations occur in cardiac muscles?
Yes
Why would cross striations occur in cardiac muscles?
Because there is interdigitation of actin and myosin
What are the types of cardiac muscles?
Atrial muscle
Ventricular muscle
Purkinje fibers
Bundle of His
What is the function of the atrial muscle?
To contract the atria
What is the function of the ventricular muscle?
To contract the ventricles
What is the function of the Purkinje fiber?
Special excitatory and conductive muscle for rhythmic conduction of nerve impulse in the heart
What is the bundle of His?
Special excitatory and conductive muscle for rhythmic conduction of impulse in the heart
What is the function of the two syncytium of the heart?
It allows atria to contract a short time ahead of the ventricle for effectiveness of heart blood pumping
What are the two syncytium of the heart?
Atrial syncytium
Ventricular syncytium
Why is it important that the atrial syncytium contracts ahead of the ventricular syncytium?
Because blood needs to go to the atrium first before being transferred to the ventricles
Where is our atrial syncytium?
In the walls of our left and right atrium
Where is our ventricular syncytium?
In the walls of our left and right ventricle
Where is the intercalated disc located?
Part of the sarcolemma and contains the gap junction and desmosomes
What is the purpose of the gap junction and desmosomes in the intercalated disc?
The gap junction is for electrical connection
The desmosomes are for mechanical connection
What is the function of the gap junction in the intercalated disc?
it forms channels between adjacent cardiac muscles
This allows ions that cause AP to travel from one cardiac cell to the next
Produces depolarization of the heart muscle
What is the function of the desmosome in the intercalated disc?
It anchors the ends of cardiac muscle cells together so the cells dont pull apart during contraction
True or False.
The mechanism of contraction of cardiac muscles, specifically atrial and ventricular are different from the smooth and skeletal muscles.
False.
Atrial and ventricular muscles contract similarly to the skeletal muscles but they have a longer duration of contraction
The RMP of atrial and ventricular muscles is from -85 to -95 and Purkinje fibers range from -90 to -100. Why do they have highly negative RMPs?
It helps to bring the cells closer to the threshold for initiating AP and allows for faster conduction of the electrical signals that regulate heartbeats
What is the conduction velocity of your atrial, ventricular, and Purkinje fibers?
0.3 - 0.5 m\sec
True or False.
The myosin and actin filaments of the cardiac muscles are similar to that of the smooth muscle cells.
False.
Their thin filaments contain actin, troponin, and tropomyosin which is more similar to skeletal muscle cells
What is the major source of Ca ions for cardiac muscles?
ECF
SR is minor lang
How do Ca ions enter into the cardiac muscles?
Via the T tubules and L-type Ca channels
Why are T-tubules the mode of entry for Ca ions into the cardiac muscle?
Because T-tubules have high amounts of electronegatively charged mucopolysaccharides that can bind to a high amt of Ca ions
What is an L type calcium channel?
A voltage gated ion channel that refers to the “long-lasting” or sustained opening of the channels during an action potential
Where can we find these L type Ca channels?
In the sarcolemma
Outline the mechanism of action for these L type Ca channels?
- Activation via AP opens the channel
- Upon opening, Ca ions flow into the cardiac cell
- Influx of calcium triggers Calcium-induced calcium release (CICR) from the sarcoplasmic reticulum. This triggers contraction
- Prolonged contraction or plateau phase
Why are L type channels important in a clinical context?
Because they can be the target for certain heart medications like calcium channel blockers
What is the difference in the SR and TT arrangement of cardiac muscle cells and skeletal muscle cells?
SR are few and less developed
TT runs along the Z-discs
They form DIADS instead of TRIADS
Why is the DIAD arrangement so important for muscle contraction?
Because the depolarization spreads down the T-tubules which is adjacent to the SR
The depolarization can open the Ca-release channels in the SR
What makes the DIAD structure so different?
It means that it can only spread the depolarization towards one terminal cisterna of a SR
This improves the coordinated heartbeat
Where does AP start in the heart?
At the SA (sinoatrial) node for the atrium
At the AV (atrioventricular) node for the ventricles
What makes the AP of the cardiac muscles different?
It has a longer AP because of the plateau
What does the plateau indicate in the cardiac AP?
The opening of slow Ca-Na channels
Although the AV node is found in the left atrium, it is responsible for AP in the ventricles. How is it able to send signals to the ventricles?
Through the atrioventricular bundle or the Bundle of His and the Purkinje fibers
