Skeletal Muscle Physiology Flashcards
1
Q
Isotonic contraction
A
Isotonic: Once the muscle has developed enough tension to move the load, the tension remains constant and muscle shortens.
- Shortening of muscle
- Movement of load
- Tension > load
2
Q
List skeletal muscle types by increasing fiber diameter
A
Slow oxidative (small)
Fast oxidative (Intermediate)
Fast glycolytic (large)
3
Q
What are the components of a triad?
A
1 T-tubule + 2 terminal cisterns of the sarcoplasmic reticulum
*The triad association is important for the contraction of the skeletal muscle because it is couple to the release of calcium.
4
Q
What activities are each skeletal muscle type most suited for?
A
Slow oxidative
- Endurance type activities
Fast oxidative
- Sprinting, walking
Fast glycolytic
- Short term interse or powerful movements
5
Q
What does a motor unit consist of?
A
A somatic motor neuron plus all the skeletal muscle fibers it stimulates.
6
Q
What are the two methods of generating graded responses?
A
Temporal summation: An increase in the tension developed in a skeletal muscle fiber caused by an increase in the frequency of action potentials.
Motor unit recruitment
7
Q
Molecules found in skeletal muscles that contain enzymatic material for glycolysis
A
Glycosome
8
Q
What is troponin?
A
A complex of 3 proteins that bind to actin, tropomyosin, and calcium
9
Q
What are the stabilizing filaments of muscle?
A
Titin
Nebulin
Myomesin
Dystrophin
10
Q
Each axon terminal innervates _______ muscle fiber.
A
One
11
Q
Bulbous end regions of the sarcoplasmic reticulum are called_____________
A
Terminal cisterna
12
Q
Myasthenia gravis
A
- Autoimmune disease: antibodies to nicotinic acetylcholine receptors inhibit contraction.
- Chronic inflammation of MG causes structural changes of the neuromuscular junction.
- flattening out of the junctional folds
- Don’t function well
- spreading out of AChR and Acetylcholinesterase
- 66% decrease in number of AChR
- an increased junctional gap.
- flattening out of the junctional folds
13
Q
Once the acetycholine is released, and it binds to its receptors, ion channels are opened. Are these ion channels specific? What do they allow for?
A
Ion channels are not specific. It allows sodium and potassium ions to flow through and down their gradients. Sodium flows into the cell and potassium flows out.
NOTE: Sodium flows much faster than potassium, so this will lead to depolization at the motor end plate.
14
Q
Why is it that another AP can be generated shortly after the muscle has started to contract?
A
Muscles AP lasts for a short time and it’s almost finished before the muscle even begins to twitch, meaning that another AP can be generated shortly after the muscle has started to contract.
* These conractions can therefore be summated in skeletal muscles.
15
Q
When you contract the sarcomere the ___________ disappears.
A
H-zone
16
Q
End plate potential .vs. action potential
A
EPP (generator potential)
- Ligand gated channels
- Charge carriers are Na+, K+
- Passive repolarization
AP
- Voltage gated channel
- Charge carrier for depolarization is Na+
- Repolarization due to increased K+ conductance
17
Q
How do you generate a stronger force using motor unit recruitment?
A
- Each motor unit requires a different stimulus. If you have a stimulus that stimulates all at once, you have a stronger force opposed to a stimulus that only stimulates one motor unit.
- Increasing the amount of stimulus coming from upper motor neurons increases the amount of lower motor neurons that are activated.
- This increases the amount of cells that contract and increase the overall contraction of the muscle.
18
Q
How is ATP regenerated?
A
Phosphorylation of ADP by creatine phosphate (CP)
Generates 1 ATP per CP
Does not require oxygen
Provides 15 sec. of energy
Glycolysis
Generates 2ATPs per glucose
Does not require oxygen
Fast process
*Fast twitch fibers tend to use these two methods
Aerobic respiration in mitochondria (citric acid cycle)
- Generates 30-32 ATPs per glucose or FA
- Slow process
•Dependent on oxygen
*Slow twitch fibers use this method
19
Q
Basic contractile unit of skeletal muscle
A
Sarcomere
20
Q
What properties of muscle fibers determine twitch activity?
A
- Muscle properties such as:
- # of blood vessels
- Whether or not they have mitochondria
- Whether or not they use aerobic respiration
*There are different variants of myosin in our bodies that are genetically determined
21
Q
What is the function of tropomyosin?
A
Blocks the myosin-binding site, when the muscle is at rest
22
Q
What are three factors which affect the development of muscle tension?
A
1. Frequency of stimulation
2. Number of motor units recruited
3. Degree of muscle stretch
NOTE: We don’t need to generate maximum force in our muscles at all times. Less force for lighter things. More force for heavier things.
23
Q
Strings of G- actin produce _____________
A
F- actin
24
Q
The synaptic cleft of the neuromuscular junction is rich in __________ and ____________.
A
Glycoproteins and collagen fibers.
*The glycoproteins help keep neurotransmitters in the cleft just a little bit longer before being degraded by acethylcholinesterase.
25
What is treppe?
A gradual increase in tension due to a certain stimulus frequency
26
Adaptations to aerobic exercise leads to...
* Leads to increase in muscle capillaries, number of mitochondria and myoglobin synthesis.
* Results in greater endurance, strength, and resistance to fatigue
* May convert fast glycolytic fibers into fast oxidative fibers
\* You can't change slow to fast twitch becuase you can't change the myosin activity
27
Is their an axon hillock in muscle cells?
No
\*Outside of the **motor end plate** is where you'll find the sodium and potassium voltage-gated channels
28
Active tension is due to binding between _____ and \_\_\_\_\_\_\_\_. Force generated can be limited by the \_\_\_\_\_\_\_\_\_\_.
Actin
Myosin
starting point
29
Explain steps to propagation of action potential
1. An end plate potential is generated at the neuromuscular junction
2. Depolarization: Generating and propagating an action potential (AP). The depolarization current spreads to adjacent areas of the sarcolemma. Voltage-gated Na+ channels open. Na+ enters cell and initiates the AP.
3. Repolarization occurs as Na+ channels close (inactivate) and voltage-gated K+ channels open. K+ diffuses rapidly out of the muscle fiber.
30
What is the function of synaptotagmin?
* Binds Ca2+
* Initiates fusion of vesicles with the docking areas/ SNARES, allowing for release of acetylcholin
31
At what point does the force generation reach its peak?
When all of the troponin C molecules are bound to calcium.
32
Each muscle fiber has specialized region of sarcolemma with junctional fold containing \_\_\_\_\_\_\_\_\_\_\_\_.
Ach receptors
33
What is the relationship between length and tension, in active tension?
* If you **overcontract** the muscles, the actin in the middle begins to overlap. When they overlap they begin to cover up **myosin-binding sites**.
* If you **stretch** the muscle, we get an "overlap" between myosin and actin that is no longer ideal becuase you have myosin heads that **no longer have actin to bind to.**
34
Why can each muscle cell only be innervated by one motor neuron?
In skeletal muscle each muscle cell is innervated by one neuron because it only has **one motor end plate**, so there's only ONE region on the skeletal muscle cell that is innervated.
\*That one end plate has to be enough to activate that cell at that one muscular junction
**NOTE:** This is very different from neurons that can have inhibitory post synaptic junctions and excitatory post synaptic junctions.
35
How is a skeletal muscle fiber stimulated to contract?
Glutamate is released from upper motor neurons to stimulate lower motor neurons. Once stimulated lower motor neurons secrete acetylcholine.
36
At shortened lengths, what contributed completely to total tension?
Active tension
\*All force is generated actively
37
The ___________ receptor is found on the T-tubule and the ____________ is found on the SR.
Dihydropyridine; ryanodine
\*The dihydropyridine and ryanodine receptors interact when an AP is proprogated. A conformational change happens with DP receptors that causes RD receptors to open. This allows for the release of Ca2+ into the cytosol.
38
Total tension=\_\_\_\_\_\_\_\_\_\_
Active tension + Passive tension
(a)At shortened lengths all force is generated actively.
Total tension = active tension
(b) As the muscle fiber is stretched beyond its resting length, passive tension begins to contribute to the total force.
Total tension = Active + passive
(c)If the muscle is further stretched, passive tension accounts for most of the total force.
Total tension = passive tension (almost)
39
What steps follow the formation of actin-myosin cross bridge?
1. **Cross bridge formation.** Energized myosin head attaches to an actin myofilament, forming a cross bridge.
2. **The power (working) stroke.** ADP and Pi are released and the myosin head pivots and bends, changing to its bent **low-energy state.**
* As a result it pulls the actin filament toward the M line.
3. **Cross bridge detachment**. After ATP attaches to myosin, the link between myosin and actin weakens, and the myosin head detaches (the cross bridge “breaks”).
4. **Cocking of the myosin head.** As ATP is hydrolyzed to ADP and Pi, the myosin head returns to its prestroke high-energy, or “cocked,” position. \*
40
The voltage stimulus that produces the initial contraction is called the \_\_\_\_\_\_\_\_\_\_\_\_\_\_
threshold stimulus.
41
\_\_\_\_\_\_\_\_\_\_\_\_ is a low-affinity, high capacity Ca2+ binding protein, within the terminal cisternae, keeps [Ca2+] in the SR.
**Calsequestin**
\*Most of Ca2+ is stored throughout the entire SR but there is a higher concentration in the **terminal cisterna** becuase of the presence of calsequestrin, which binds to Ca2+
42
What happens once Ca2+ is released into the myoplasm?
Calcium binds to troponin- C in the skeletal muscle cell. Once Ca2+ binds it causes a conformational change in troponin C that causes tropomysosin to move from the binding site (it was covering up actin). Now myosin can bind.
43
What is muscle fatigue? How and why does it occur?
Muscle fatigue is the physiological inability to contract despite continued stimulation.
* Occurs when
* Ionic imbalances (K+, Ca2+, Pi) interfere with E‑C coupling
* **Decreased release of calcium from SR**
* ATP generation via glycolysis produces **increases in [H+]**. Decrease pH has been demonstated to:
* reduce the affinity of troponin for calcium.
* Reduce myosin ATPase activity
**NOTE:** Muscle fatigue is **NOT** about using up ATP
44
Are smaller or larger motor units more excitable?
**Small motor units** (small fibers) are more excitable (lower threshold stimulus) than large motor units.
## Footnote
Smallest motor units have slow oxidative fibers (slow twitch)
Larger motor units have fast glycolytic fibers (fast twitch)
45
What is the difference between an AP of skeletal muscle fiber and cardiac muscle fiber?
_Skeletal muscle fiber_
* AP pretty much done before muscle contracts
* Refractory period is short
* This means that skeletal muscle can undergo summation and tetanus, via **repeated stimulation**
_Cardiac muscle fiber_
* Long AP
* Tension in muscle develops way before action potential is over
* AP repolarization and muscle relaxation occur almost at the same time
* Cardiac muscle CAN NOT sum action potentials or contractions can't be tetanized
46
What is passive tension?
Our muscles also have passive tension. This is due to **titin molecules (that have an elastic recoil force).**
* Titin helps to stabilize and prevent overstretching of sarcomere.
47
A stimulus strength that recruits all motor units is the \_\_\_\_\_\_\_\_\_\_\_\_
maximum stimulus
48
What is the function of myomesin?
Binds myosin and titin at M line
\*The M line is the midline of the sacromere
49
What are the 3 phases of a muscle twitch?
**Latent period**:
* follows stimulation
* Excitation-contraction coupling begins
* No measurable muscle tension developed
**Period of contraction**:
* Cross bridge formation occurs
* Tension develops
**Period of relaxation**
Ca2+ reentry into the SR
Tension declines
50
What is needed for muscles to relax?
* Ca2+ needs to reenter the SR
* This is done by **ATP-DEPENDENT** sacro pumps on the surface of the SR
* Once the calcium is taken back in and its no longer in the cytosol, the muscle can relax
\*There are also pumps on the surface of muscle cell membrane (sarcolemma) that can pump Ca2+ out into ECM
51
The tension that you feel when you try to stretch your muscles is due to which protein?
**Titin**
* Titin trys to pull sacromere back to ideal length
52
Incomplete tetanus
Maximum contractions, but, muscle relaxes slightly between contractions creating a **quivering effect**
**\***Muscle fibers do not completely relax before the next stimulus because they are being stimulated at a fast rate; however there is a partial relaxation of the muscle fibers between the twitches
53
What are the components of the thin filament?
Actin
Tropomyosin
Troponin
54
in the absence of ATP, myosin heads will not detach from actin, causin \_\_\_\_\_\_\_\_\_\_\_\_.
Rigor mortis
55
During muscle shortening, the heads of the myosin filaments pull the actin filaments inward toward the \_\_\_\_\_\_\_\_\_\_. This action\_\_\_\_\_\_\_\_\_\_\_\_ (increases/ decreases) the area of overlap between the thick (myosin) and thin (actin) filaments.
M line; increases
56
Explain the steps to excitation at neuromuscular junction
1. **Action potential** arrives at axon terminal of motor neuron.
2. **Voltage-gated Ca2+ channels open.** Ca2+ enters the axon terminal moving down its electochemical gradient.
3. Ca2+ entry causes **ACh to be released by exocytosis**.
4. **ACh diffuses across the synaptic cleft** and binds to its receptors on the sarcolemma.
5. ACh binding opens ion channels in the receptors that allow simultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber. More Na+ ions enter than K+ ions exit, which produces a local **change in the membrane potential called the end plate potential.**
57
Explain the interaction between dihydropyridine and ryanodine after an action potential is fired.
AP causes a conformational change to receptors in T-tubule (dihydropyridine) because of **voltage.** Because DP and RD receptors are closely related, a conformational change in DP causes a conformation change in RD that causes it to open.
58
What is the function of nebulin?
* Binds with and **stabilizes F-actin**
* Attaches to Z-disc
59
How do you get a stepwise increase in peak tension of individual fibers?
* When a muscle has been at rest for a long time and then its been stimulated to contract, you get a little bit of Ca2+ come in from the SR to get a contraction.
* If you stimulate again right after that, all of the Ca2+ thats in the cytoplasm has not been pumped out to ECM or pumped back into SR yet, so this lingering Ca2+ in addition to the bolus of calcium coming in upon the second stimulus will cause an increase in tension.
* Each time there's a stimulus right after relaxation, you build upa residual calcium, until you reach a **maxpoint/ plateau**, where you have enoigh Ca2+ to where **all of troponinc C molecules are attached to calcium.** This is the largest force you can get for that **single motor unit.**
* If you want to get that muscle to contract even more you have to stimulate additional motor units.
60
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ breaks down Ach.
Acetylcholinesterase
61
What is different in the innervation of muscle cells and neurons?
* When it comes to neurons, they can innervate and be innervated by several neuron.
* When it comes to muscle cells, they can only be innervated by one neuron.
* However when it comes to **motor units,** neurons can innervate several muscles cells.
\*So you can have an upper motor neuron that innervates mor than one lower motor neuron. One lower motor neuron can be innervated by several different upper motor neurons.
62
What is the importants of the essential component of the light chain?
The essential component can be phosphorylated and can direct how the head moves in addition to how quickly it moves.
\*This regulation is important in cardiac and smooth muscle, not so much in skeletal
63
Complete tetanus
Contractions maximal, smooth and sustained
\***No relaxation** of the muscle fibers between stimuli and it occurs during a high rate of stimulation.
**\*A fused tetanic contraction is the strongest single-unit twitch in contraction.**
64
Lower motor neurons innervate \_\_\_\_\_\_\_\_\_\_\_\_\_, while upper motor neurons innervate\_\_\_\_\_\_\_\_\_\_\_.
Skeletal muscle; one or mor lower motor neurons in the spinal cord
65
Define tension and load.
**Muscle tension**:
The force generated by a contracting muscle
**Load**:
The force opposing the contracting muscle
66
As a muscle is stretched beyond a critical length (ideal length) tensions builds as an ___________ function.
exponential
67
Where are upper motor neurons located? What about lower motor neurons?
Upper motor neurons are located in the motor cortex. Lower motor neurons are primarily located in the spinal cord (ventral horn)
68
Why are slow twitch fibers red?
* High levels of myoglobin
* High levels of blood vessels
69
We have muscle tone in all of our muscles because of \_\_\_\_\_\_\_\_\_\_\_
**Spinal reflexes**
\*There is a sensory input from muscle stretch receptors. Groups of motor unit are activated in response to input from stretch receptors.
70
Why are small motor units more excitable than large motor units?
Because they have a lower threshold stimulus
**REMEMBER:** The threshold stimulus is the voltage stimulus that produces the initial contraction, so small motor neurons require a small voltage to illicit a contraction
71
Where are the cell bodies of lower motor neurons located? Where do the axons of lower motor neurons exit?
* **Cell bodies** of lower motor neurons are located in the **ventral horn** of the spinal cord.
* **Axons** exit the spinal cord via the **ventral root** and project in spinal nerves to innervate target muscles.
72
What effect does the load have on duration and velocity of a contraction?
The greater the load, the less the muscle shortens and the shorter the duration of contraction
73
In which type of contraction is tension less than load?
Isometric
74
What is the function of titin?
* Connects **myosin to Z line**
* Stabilizes myosin and **protects from over stretch**
* Responsible for **muscle flexibility**
\*Titin is elastic and can extend from the Z- disc and run through the core of the myosin filament
75
In ___________ contraction the muscle shortens. In ____________ contraction the muscle lengthens.
Concentric; eccentric
76
What is the recruitment order for the three skeletal muscle types?
1st: Slow oxidative
2nd: Fast oxidative
3rd: Fast glycolytic
77
How does the end plate potential undergo passive repolarization?
The ligand gated channels don't stay open forever and the Ach also gets metabolized
78
What is the function of titin?
It stabilizes myosin to the Z line
79
Skeletal muscles are innervated by motor neurons that emanate from the spinal cord. Can our skeletal muscles contract without that innervation?
No!
\*Other muscles can contract without innervation but our skeletal muscles cannot.
80
Calcium binds to what component of the SNARE complex?
Synaptotagmin
81
What is active tension?
Muscles operate with greatest **active tension** when close to an ideal length (often their resting length).
* When stretched or shortened beyond this , the maximum active tension generated decreases.
* This decrease is minimal for small deviations, but the tension drops off rapidly as the length deviates further from the ideal.
82
What is the importance of muscle tone?
* Responsible for balance and posture
* Keeps muscles firm, healthy and ready to respond
\*Muscle tone is the constant, slightly contracted state of muscles
83
What steps occur to lead to a contraction, after the action potential is fired?
1. AP propagates along the sarcolemma and down the t-tubules.
2. Receptor coupling t-tubule (Dihydropyridine receptor) to SR changes form and opens Ca2+ channels (Ryanodine receptor).
3. Ca2+ is released into the myoplasm.
4. Ca2+ binds to troponin releasing the blocking action of tropomyosin, uncovering myosin binding sites .
5. Myosin head forms binds to actin creating cross bridge.
84
What is the difference between the AP for skeletal muscle cells compared to neurons?
There is NO hyperpolarization in skeletal muscles because the resting membrane potential is lower/ more negative than potassium's equilibruim potential.
85
Z line represents \_\_\_\_\_\_\_\_\_\_\_
End of sarcomere
86
* 25-40% of energy released in muscle activity useful as \_\_\_\_\_\_\_\_
* Remaining energy (60-75%) is given off as \_\_\_\_\_\_\_\_\_
work
heat
87
As the muscle fiber is stretched beyond its resting length, __________ tension begins to contribute to the total force.
Passive
**NOTE:** If the muscle is further stretched, passive tension accounts for most of the total force.
88
I band represents \_\_\_\_\_\_\_\_\_\_\_
Actin
89
Isometric contraction
Isometric: muscle develops tension, but **muscle length does not change.**
Muscle does not shorten
Load is not moved
Tension \< load
\*Tension isn't enough to move the load
90
Large motor units have __________ fibers.
Fast glycolytic
91
What is the function of dystrophin?
* Maintains **structural integrity**
* Achors **actin** to the sarcolemma
\*Defienciencies and mutations linked to muscular dytrophies
92
The neurotransmitter that is released from our lower motor neuron is \_\_\_\_\_\_\_\_\_\_\_\_; the receptors it binds t on skeletal muscle is \_\_\_\_\_\_\_\_\_\_\_\_. The neurotransmitter that is released from upper motor neurons is \_\_\_\_\_\_\_\_\_\_\_; the receptor that it binds to on lower motor neurons is \_\_\_\_\_\_\_\_\_\_\_\_\_.
Acetylcholine; Nicotinic
Glutamate; glutamatergic
93
Thick filaments: \_\_\_\_\_\_\_\_\_\_\_
Thin filaments: \_\_\_\_\_\_\_\_\_\_
Myosin
Actin
94
What is considered a muscle twitch?
* Motor unit's response to a **single action potential** of its motor neuron
* Simplest contraction observable in lab (recorded as **myogram**)
95
What happens after the membrane is depolarized?
If the depolarization is strong enough to cross the threshold, it will lead to the firing of an action potential.
**NOTE:** The threshold is the point at which **voltage-gated channels** are activated. You _won't_ get an AP with ligand gated channels. You will only get an AP with voltage-gated channels
96
Characteristics of Skeletal, Cardiac, and Smooth Muscle
Skeletal
* Striated & Voluntary
* Requires somatic nervous system stimulation
* Rapid contractibility & high fatigability
Smooth
* Smooth & Involuntary
* Stimulated by ANS, hormones, stretch & pacemaker cells
* Slow, sustained contractions & low fatigability
Cardiac
* Striated & Involuntary
* Self initiated stimulation & ANS modification
* Continuous contraction/relaxation & No fatigability
97
What are the two myosin protein chains? What are characteristics of each?
Myosin has 2 types of protein chains.
* Heavy chains
* Has ATPase activity
* Binds to actin
* Light chains
* Essential
* Regulatory
98
O2 storage unit in muscles
Myoglobin
99
Skeletal muscles use ATP for contraction and relaxation. In what way?
* Cross bridge attachment and detachment
* Calcium pumps in the sarcoplasmic reticulum
* Na+/K+ pumps that return sarcolemma to resting conditions.
**NOTE:** Cellular stores of ATP are limited and depleted within 6 seconds of contraction.
100
How does botulinum toxin work?
* Works by **blocking the exocytosis of Acetylcholine**
* ****disrupts the function of SNARE proteins
* It degenerates/ cleave the SNARE proteins, thereby inhibiting the release of the vesiscles.
\*Short-lived because SNARE proteins just grow back
101
What is the relationship of action potention to tension development in skeletal muscle?
The AP you trigger the more fibers that will be stimulated, which will increase the tension development of the WHOLE muscle
\*Each time a skeletal muscle is stimulated it builds tension until it reaches a plateau, at which point you won't get an increase in tension with the same level of frequency of stimulation.
102
What is excitation- contraction coupling?
E-C coupling is the sequence of events by which the initiation of an action potential along the sarcolemma leads to the contraction of myofilaments.
103
A band represents\_\_\_\_\_\_\_\_\_\_\_\_
Myosin
104
Cardiac muscle cannot sum action potentials or contractions and can't be tetanized. Why is this important?
The heart keeps the rhythm, fils up with blood, and then pumps it out. The heart needs to be able to refill with blood and then supply the body with blood
105
Contratile units of muscle
Myofibrils
106
What are the three skeletal muscle types?
Slow oxidative fibers
Fast oxidative fibers
Fast glycolytic fibers
107
Small motor units have _________ fibers.
Slow oxidative
108
Duchenne Muscular Dystrophy
* X- linked, recessive disease
* Caused by a **mutation in the dystrophin gene** (largest gene on the X-chromosome).
* Causes **loss of structural stability of myocytes.**
109
In which type of contraction is tension greater than load?
Isotonic
110
What are some characteristics of motor unit fibers?
* Fibers of an individual motor unit are **dispersed throughout the muscle.**
* Stimulation of a single motor unit causes a weak contraction of the entire muscle.
* Fibers of a single motor unit **contract in unison.**
* Fibers of single motor unit are **all the same type**.
**NOTE:** One muscle may have many motor units of different fiber types
111
It is at the _____________ that a motor neuron is able to transmit a signal to the muscle fiber, causing muscle contraction.
neuromuscular junction
112
Which components of the sarcomere shorten with contraction?
H zone and I band
