Lecture 12: Skeletal Muscle Flashcards

Exam 2

1
Q

Skeletal muscle is the largest _____?

A
  • The largest contributor to body weight and volume in non-obese people
  • Largest container we have within the body
  • Need them to behave normally otherwise things get screwed up, very important
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2
Q

How can anesthetics affect skeletal muscle?

A

We take a lot of skeletal muscles offline with anesthetics
- Volatile anesthetics - reduce amount of muscle activity
- Paralytics - take the skeletal muscles offline

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3
Q

What are the 8 roles of skeletal muscle

A
  • Largest contributor to body weight and volume in non-obese people
  • Locomotion
  • Expression
  • Communication
  • Body temp
  • Storage of glycogen
  • “Effectors”/neural targets
  • Large store of ions, fluid, and proteins
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4
Q

The vast majority of skeletal muscle cells are innervated by how many motor neurons?

A

Just one
One motor neuron can innervate multiple skeletal muscle cells, very large and branch multiple times

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5
Q

A collection of muscle fibers

A

Motor unit

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6
Q

What is an example of a skeletal muscle cell that is innervated with more than one motor neuron?

A

ocular muscles in the eye socket

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7
Q

Where are the cell bodies of motor neurons located?

A

The anterior horn of the grey matter of the spinal cord

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8
Q

A single neuron that innervates a motor unit

A

Motor Neuron
- Small mu’s=small mn’s
- Large mu’s=large mn’s

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9
Q

What are the 2 ways to excite motor neurons?

A
  1. Descending spinal pathways originating from the brain
  2. Reflex arcs - sensory info fed into the back of the cord that results in a muscle contraction at the same level of the spinal cord (without traveling back to the brain) so that muscle contraction can occur quickly to withdraw from pain
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10
Q

What is another name for a skeletal muscle cell?

A

Muscle fiber

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11
Q

What are the contractile elements of skeletal muscle cells? How are they arranged?

A

Actin and myosin filaments - arranged in tube-like structures

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12
Q

What is the specialized version of the ER called in skeletal muscle cells?

A

Sarcoplasmic reticulum - sarco = muscle, more developed ER

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13
Q

Where do skeletal muscle cells store Ca++?

A

The sarcoplasmic reticulum - needs Ca++ for contraction (release internally)

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14
Q

What are transverse tubules? Why are they needed?

A

An extension of the skeletal muscle cells that allows an AP to move deep into the muscle cells (enfolding); invaginations of the cell membrane
Needed because skeletal muscle cells can be very long (can be over a foot long) and are fairly wide/thick

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15
Q

What are the 4 components of skeletal muscle cells

A
  • Sarcoplasm
  • Sarcoplasmic reticulum
  • Transverse Tubules - AKA T Tubules
  • Actin/myosin filaments
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16
Q

What do we need to know for exam 2 about sarcomere anatomy?

A

Just need to know that contraction shortens the muscle

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17
Q

Fluid inside muscle cells (like cytoplasm)

A

Sarcoplasm

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18
Q

What are the structures noted in the picture

A

Microscopic view of skeletal muscle cells
- Each branch of motor neurons takes care of innervation for skeletal muscle fibers
- Each fiber has NMJ associated with it (balls in pic)
- Some only have one motor neuron for several skeletal muscle cells
- Have zebra-like (cross-hatch) pattern because of actin and myosin filaments

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19
Q

What are the invaginations that increase N-M junction surface area?

A

Clefts

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20
Q

What are the 2 types of clefts on the skeletal muscle cell?

A
  • Primary: only one enfolding
  • Secondary: more than one enfolding
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21
Q

What is located in the membrane of skeletal muscle clefts?

A

ACh receptors towards the surface of the cleft, closer to the neuron
Concentrated V-G Na+ channels on the inside of clefts and the other side of ACh-R

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22
Q

What surrounds motor neurons?

A

Wrapped in myelin, maintained by Schwann cells that hang out at the terminal end of motor neurons; Schwann cells manage the myelin in the motor neuron back to the spinal cord

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23
Q

What is the role of mitochondria in the NMJ?

A

The skeletal muscle cells and motor neurons both have a lot of mitochondria located near the NMJ

mitochondria in the presynaptic terminal produce acetate. Acetate combines with recycled choline into acetylcholine (ACh)

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24
Q

How many ACh-R are there? How many are activated during an AP? How much ACh is needed?

A

ACh receptors - have 5 million at each NMJ
- About 500,00 activated during a typical AP ~10%
- Need to be producing at least 1,000,000 ACh from motor neuron - usually twice that in reality

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25
Q

Why is more ACh released than what is needed by the motor neuron?

A
  • Some get broken down by AChesterase before reaching receptors
  • Some bind to receptors and only have 1 ACh molecule bound and therefore can’t activate the receptor (need 2 ACh)
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26
Q

What is the function of AChesterase?

A

Breaks down ACh via hydrolysis (ACh → acetyl + choline)
Once broken down to acetyl and choline, no more effect on the ACh receptors
Limits length of depolarization from motor neuron - finite time period so resetting can happen

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27
Q

What does the motor neuron do with acetyl and choline after AChesterase breaks apart ACh?

A

Choline is moved back into motor neuron via choline-sodium transporter and Choline ATPase pumps
Acetyl recycled too but not as much known about mechanism

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28
Q

Where is AChesterase produced and housed?

A

Produced by the skeletal muscle and fastened to skeletal muscle at the NMJ

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29
Q

What are other ways to describe acetyl?

A

Acetate, a very small starch group

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30
Q

How are acetate and choline made in the motor neuron?

A
  • Mitochondria produces acetate and ATP
  • Can store extra choline in cell wall (phosphatidylcholine)
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31
Q

What is underneath the NMJ and clefts in the skeletal muscle?

A

Contractile elements - myosin and actin

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32
Q

Why doesn’t K+ want to exit the skeletal muscle cell through open ACh-R, even though it can?

A

K+ probably would want to leave via leak channels instead (easier)

33
Q

How many subunits are there on nACh-R?

A
  • 2 Alpha subunits - Both alpha subunits must bind ACh to open the ion channel
  • 1 Beta subunit
  • 1 Delta subunit
  • 1 Epsilon subunit
34
Q

What is the name of the first nACh-R antagonist? Where was it found?

A

Curare - paralytic found in rainforest, used to paralyze prey; not used clinically now
- Most non-depolarizing muscle relaxant (NDMR) paralytics are modeled after Curare MOA
- Only need one to bind to each receptor to block the channel, antagonist; stop AP from starting in the skeletal muscle

35
Q

How does ACh leave the motor neuron? What is this mediated by?

A

Exocytosis, mediated by Ca++
(SNAP and SNARE proteins)

36
Q

What are the components of skeletal muscle calcium signaling?

A
  • SR Calcium Release
  • Depolarization
  • Repolarization
  • Ryanodine (RyR) Receptors
  • SERCA pumps
37
Q

What are the different types of channels seen in a skeletal muscle cell?

A

Same as normal cell -
V-G Na+ channels
V-G K+ channels
K+ leak channels
Na+ leak channels (less than K+)

38
Q

What are the channels that cause an AP in a skeletal muscle cell?

A

Same as normal cell -
V-G Na+ channels
V-G K+ channels

39
Q

How do skeletal muscles know when to respond to an AP?

A

DHP (dihydropyridine) receptors that sense the voltage changes in the cell wall
- Not really a receptor but a sensor

40
Q

How do DHP receptors respond to a change in voltage?

A

Voltage sensor senses AP → has physical connection to Ca++ release channel on SR - tugs on attachment (looks like a spring), removing obstruction from Ca++ being released (pops the cork), liberating Ca++ to inside skeletal muscle → contraction with actin and myosin
- some Ca++ comes from outside cell too

41
Q

Where are SRs located?

A

Fairly close to the cell wall, close to T-tubules
- SR is the yellow portion surrounding the T-tubules

42
Q

Where are DHP receptors located?

A

In cell wall and in T-tubules

43
Q

Some Ca++ channel blockers are _______

A

dihydropyridine Ca++ channel blockers

44
Q

DHP receptors look a lot like what?

A

V-G Ca++ channel; lets Ca++ in from SR instead of outside of the cell
However a small amount of Ca++ comes from outside cell too

45
Q

What is the name of the Ca++ release channel on the SR?

A

Ryanodine (RyR) Receptors

46
Q

What chemicals are RyRs sensitive to?

A

ryanodine

47
Q

Are RyRs receptors?

A

Not really a receptor in function in the body because it is physically attached to DHP receptor
Called receptors because they open in response to ryanodine binding

48
Q

How does the Ca++ get put back into the SR after an AP?

A

SERCA pumps - sarcoendoplasmic reticulum calcium ATPase (SERCA) pump
- need ATP because Ca++ going against the concentration gradient

49
Q

What are the steps to skeletal muscle E-C coupling?

A
  1. Motor neuron depolarizes (from brain or reflex arcs)
  2. Ca++ influx into motor neuron (P-type Ca++)
  3. ACh vesicles fuse to presynaptic neural cell wall/membrane
  4. ACh secreted by presynaptic neuron (into NMJ)
  5. ACh interacts with nACh receptors
  6. Na+ comes in (#1); Ca++ comes in (#2)
  7. Local Na+ and Ca++ influx generates end plate potential (EPP)
  8. EPP in a physiologic “setting” always causes an action potential in skeletal muscle; Local depolarization→AP
  9. Action potential spreads down muscle fibers in both directions (←AP→) via V-G Na+ channels
  10. Muscle depolarization sensed by dihydropyridine “receptors”/sensors (DHP)
  11. Dihydropyridine sensors pull on ryanodine receptors (RyRs)
  12. Ca++ influx into sarcoplasm
  13. After AP, Ca++ tucked back into SR via SERCA, then muscle stops contracting
50
Q

When does a skeletal muscle stop contracting?

A

Once Ca++ tucked away back into SR

51
Q

What is the local depolarization that generates an AP called? Where does it occur?

A

End plate potential (EPP) - NMJ
- Occurs when nACh-R opens and allows local Na+ and Ca++ influx

52
Q

What is myasthenia gravis?

A
  • Condition where the patient’s body generates antibodies to nACh-R
  • Immune system response to inflammation or genetic anomaly with thymus gland
  • Gets worse throughout the day (better in the morning, worse in the evening)
53
Q

How does myasthenia gravis affect skeletal muscle?

A

Antibodies park themselves on top of nACh-R
- The immune system comes in and destroys receptors
- Over time, clefts become scarred over
- Fewer nACh-R and V-G Na+ channels
- Can’t fire an AP

54
Q

What are the treatments for myasthenia gravis?

A
  1. Remove thymus gland
  2. Plasmapheresis
  3. Acetylcholinesterase inhibitors (-stigmine)
55
Q

How does plasmapheresis work to treat MG and LEMS? What’s the downside?

A

Plasmapheresis removes circulating antibodies
- can’t just remove one type of antibody from blood → can be bad

56
Q

How do acetylcholinesterase inhibitors treat myasthenia gravis?

A

Inhibitor AChesterase, keeping ACh around longer, increasing the likelihood of ACh binding to receptors

57
Q

Why can’t acetylcholinesterase inhibitors be used to treat LEMS?

A

There’s no ACh in the synapse because P-type Ca++ channels are attacked, so ACh is never released from motor neuron

58
Q

What is LEMS or ELMS?

A

Lambert-Eaton Myasthenic Syndrome
- Parody of plastic (paraneoplastic) syndrome - develops after cancer (especially lung cancer)
- Antibodies to P-type Ca++ channels, preventing ACh release from vesicles

59
Q

What are the treatment options for LEMS?

A
  1. Plasmapheresis
  2. Remove lung tumor
  3. Drugs to block K+ channels
60
Q

Drugs used to treat LEMS are fairly _____

A

dangerous - V-G K+ channel blockers unsafe because not specific for muscle cells only → cardiotoxic

61
Q

________ isn’t a good K+ channel blocker

A

Amiodarone - fairly safe because not very good

62
Q

How do drugs used to block K+ channels treat LEMS?

A

K+ prevented from leaving cell → more positive membrane potential → longer depolarization of motor neuron → allows more time for Ca++ to come in through P-type Ca++ channels → increasing ACh release

63
Q

How do P-type Ca++ channels work?

A

Don’t have an inactivation gate
- Open when cell depolarized, closed when cell is repolarized

64
Q

What are the drugs that are used to treat LEMS?

A

TEA - tetra-ethyl ammonium
4,5-diaminopyrimidine

65
Q

When is LEMS treated with K+ channel blockers?

A

End stage, nothing can be done about the tumor

66
Q

Succinylcholine includes

A

2 ACh

67
Q

The two types of paralytics are

A

depolarizing and non-depolarizing

68
Q

Succinylcholine is a _______ paralytic

A

depolarizing

69
Q

How long does succinylcholine last?

A

10 min, longer than ACh

70
Q

The initial muscle twitch when giving succinylcholine is called _______

A

fasciculation
Initially, opening of nACh-R causes a depolarization wave → generating a contraction or fasciculation (initial muscle twitching/quiver), because the drug hits different parts of the muscle at different times

71
Q

Succinylcholine acts to paralyze the muscle by

A

Sustained depolarization of the skeletal muscle via binding to nACh-R and keeping them open for prolonged period of time, causing constant Na+ leaking into skeletal muscle, preventing V-G Na+ from resetting

72
Q

How does sux cause Na+ to constantly leak into the skeletal muscle?

A

All the V-G Na+ channels in the area are stuck in the inactive configuration because the activation gate won’t close, until repolarization happens

73
Q

nACh-R are only found in the ____

A

NMJ, nowhere else in skeletal muscle
Ends of the skeletal muscle farther away, so only small area of skeletal muscle is paralyzed

74
Q

Can AChesterase break down sux?

A

AChesterase is specific for breaking ester bonds in ACh, can’t destroy succinylcholine (2 ACh) in the same way

75
Q

What is different about a stroke patient’s skeletal muscle? What would be the consequences of giving sux?

A

Sustained (+) inside cell causes more K+ to leak out of cell (trying to repolarize) → leaking K+ in the blood increases by K+ levels by 0.5 mOsm/L, okay in healthy individuals

Unhealthy skeletal muscles (denervation injuries or stroke) - generate more nACh-R in places other than just the NMJ → more K+ leaking, widespread → hyperkalemia → heart problems

76
Q

Differentiate between P-type and L-type Ca++ channels

A

P-type - primarily found in the motor neurons, don’t have inactivation gate (open when depolarized, closed when repolarized)
L-type - found in the heart and smooth muscle cells, takes longer to open and close (do have them on motor neurons but not needed for ACh release)

77
Q

T/F: V-G K+ channels are required for repolarization

A

F - repolarization mostly via K+ leak channels, but V-G K+ make the process faster

78
Q

LEMS symptoms get _____ with activity

A

better