Skeletal Muscle Physiology (Week 1--Homsher) Flashcards

1
Q

Skeletal muscle fibers

A

Large diameter (20-100um)

Long (2mm - tens of cm, almost entire length of muscle)

Multi-nucleate

Contain regenerative satellite cells

T-tubules smaller and sarcoplasmic reticulum as much as 7% of cell volume

Much more Ca2+ and calsequestrin in skeletal muscle

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2
Q

Costameres

A

Sub-sarcolemmal protein assemblies that contain desmin (floppy), dystrophin, gamma-actin

Connect and align Z-disk of myfibrils to each other and to dystroglycans and sarcoglycans (integral membrane proteins)

Integral membrane proteins then bind laminin, fibronectin, collagen in ECM

Costameres and dystrophin link contractile proteins and cytoskeleton to ECM and minimize damage to sarcolemma

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3
Q

Function of costameres

A

Links and aligns myofibrils with each other and transmits force and displacement occurring in them to ECM and to adjacent muscle cells

Minimizes disruption of phospholipid layer of sarcolemma when muscle length changes significantly during shortening or lengthening

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4
Q

What happens if you have absent or defective dystrophin?

A

Duchenne Muscular Dystrophy (DMD)

Working muscles damaged when try to undergo concentric and eccentric contraction and make cell membrane leaky to Ca2+ so intracellular proteases activated

Damaged muscle fibers gradually degenerate –> death

Dystrophin located in skeletal and cardiac muscles, brain and lung tissue

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5
Q

Duchenne Muscular Dystrophy (DMD)

A

Absence of or defect in dystrophin

Disease is due to lack of connection of costameres!

X-linked so only affects males (3/10,000 live births)

Working muscles damaged by concentric and eccentric contractions so cell membrane leaky to Ca2+ and intracellular proteases activated, intracellular creatine kinase appears in blood

Muscle fibers damaged faster than repair –> muscle breakdown or infiltration by macrophages, leukocytes, cytotoxic T cells –> apoptosis –> fat globules or fibrous tissue –> children to wheel chair by age 12, death from respiratory or cardiac disease in teens or 20’s

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6
Q

Becker Dystrophy

A

Expression of modified or truncated form of dystrophin and produces slowly progressive dystrophy and less severe symptoms than DMD

Myalgias, muscle cramps, reduced exercise tolerance, mild limb girdle weakness

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7
Q

What causes Ca2+ to enter the sarcoplasm in skeletal muscle to trigger contraction?

A

Depolarization of T-tubules

S4 region (voltage sensing, membrane spanning) of L-type Ca2+ channel (aka DHP receptor) is positively charged and pulls on/opens up Ca2+ pore in RyR in the SR

Ca2+ flows out of SR through RyR

Note: don’t need influx of Ca2+ across sarcolemma to initiate Ca2+ release from SR

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8
Q

Cross bridge mechanism

A

Same as in cardiac muscle but faster (>2x faster)

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9
Q

Sliding filament mechanism

A

SKM contracts and relaxes over a wider sarcomere length range (1.6 - >3um)

Force plateau from 2.25 - 2.55um

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10
Q

Calcium regulation of contraction

A

TnC in SKM contains 2 regulatory Ca2+ binding sites so full activation of SKM requires Ca2+ release at least 2x cardiac muscle

Ca2+ released from SKM SR RyRs by electro-mechanical coupling mechanism (rather than Ca2+-induced Ca2+ release in cardiac muscle)

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11
Q

Active vs. passive force

A

Active force involves cross bridge interaction, splitting ATP

Passive force is just moving muscle

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12
Q

Can skeletal muscle cells regenerate?

A

Yes, use satellite cells (stem cells)

Muscle is damaged all the time, so is important to be able to regenerate!

(this is in contrast to cardiac cells)

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13
Q

How do skeletal muscle fibers regenerate?

A

Fiber injury

Neutrophil invasion, necrosis and autolysis

Macrophage removal of necrotic tissue

Satellite cell mitosis and proliferation

Satellite cell fusion

Fusion to myotube and fusion with fiber stumps

Restoration of original fiber

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14
Q

How many muscle fibers does a single alpha-motor neuron innervate?

A

Number of muscle cells per motor unit is variable (5-2,000 separate muscle fibers)!

However, each AXON of a neuron only innervates ONE muscle fiber

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15
Q

Does the size of the motor neuron tell you how many muscle fibers it might innervate?

A

Yes, smaller motor neurons innervate fewer fibers (thus make smaller force) and larger motor neurons innervate more muscle fibers (thus make larger force)

Also means smaller current needed to initiate AP in smaller motor neuron, and larger current needed in larger motor neuron

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16
Q

How do motor neurons initiate muscle contraction?

A

Alpha-motor neuron starts in ventral horn of gray matter of spinal cord

Efferent myelinated axon to muscle fibers motor endplate

At motor endplate (highly folded series of clefts or grooved region of muscle sarcolemma), synapse where ACh released by axon terminal onto nicotinic receptors of muscle membrane

Sarcolemmal conductance to Na+ and K+ increased and membrane potential increases/depolarizes

Initiates AP in membrane adjacent to endplate by passive conduction

AP spreads over entire muscle cell membrane

Neuromuscular cleft contains lots of AChE so ACh is hydrolyzed so AP at NM junction and AP generated by muscle membrane is 1:1

17
Q

Does the SKM action potential overshoot and have a hyperpolarization phase?

A

No! It actually “undershoots” to a value more positive than resting potential then gradually returns to resting potential

18
Q

Latent period

A

5-18ms delay between beginning of muscle AP and beginning of force development

During this time, excitation-contraction coupling occurs

19
Q

Twitch

A

Mechanical response to single AP

When muscle not allowed to shorten following activation, the mechanical response is called isometric twitch

20
Q

3 different types of muscle fibers

A

Type I (slow, red): contract and relax slowly (200-500ms), shorten slowly, rely on oxidative phosphorylation to produce ATP, have smaller diameter and are dark red bc have lots of myoglobin

Type IIA (fast, red): contract and relax more rapidly (40-120ms), shorten 2-3x faster than type I fibers, are more glycolytic, do oxidative phosphorylation, red (lots of myoglobin)

Type IIB (fast, white): contract and relax more rapidly than type IIA fibers, develop more isometric force, contain fewer mitochondria so only limited oxidative phosphorylation, little myoglobin

21
Q

What are different muscle fibers used for?

A

Type I used for endurance and very fine movements

Type IIA used for endurance

Type IIB used for fast powerful contractions

Different fiber types have different isoforms of contractile proteins

Muscle fibers are very plastic: if you do endurance training, you’ll increase cross sectional area of Type I and IIA fibers and decrease CSA of Type IIB fibers

22
Q

Is there a refractory period for stimulating another action potential?

A

Yes but it is a small fraction of the twitch duration so muscle can be stimulated a number of times during the twitch

23
Q

Fused and unfused tatanus

A

Unfused tetanus: repetitive stimulation at increasing rates causes oscillatory state called unfused tetanus

Fused tetanus: muscle stimulated so many times in a row that you get smoothly rising fused tetanus

24
Q

Is stimulus frequency needed to produce fused tetanus the same in type I and type II fibers?

A

No, require greater stimulus frequency to produce fused tetanus in Type II fibers than Type I fibers because Type II fibers have higher rate of cross-bridge cycling and Ca2+ pumping

25
Q

How do we physiologically regulate the force exerted by the muscle?

A

1) Frequency of stimulation
2) Number of motor units firing
(ex: Type I fibers small and enervate small numbers of muscle cells whereas Type IIB fibers are largest and innervate large numbers of muscle cells)

26
Q

Concentric (isotonic) contraction

A

Muscle shortens as it contracts

Once muscle starts to shorten, force needed to keep it shortening decreases then levels off

ATP is hydrolyzed, walking up stairs harder than walking down…

27
Q

Eccentric (forced lengthening) contraction

A

Muscle lengthens as it contracts (oxymoronically!)

Force rises rapidly as muscle is lengthened, to twice that produced by isometric contraction

However, rate of energy consumption during eccentric contraction is very small because muscle hydrolyzes very little ATP (work done on muscle produces force in cross bridge and reverses power stroke and detaches actomyosin attachment before Pi and ADP released) (think of it as a mechanical force breaking cross bridge so no ATP has to be hydrolyzed–cheating!)

This is why walking down stairs much less tiring than walking up stairs (reduced rate of enegy expenditure)

28
Q

Delayed onset muscle soreness (DOMS)

A

Most frequently occurs in “weekend athlete” or people who only infrequently exercise and then perform strenuous exercise

8-24 hours after exercise, muscles sore and limb motion limited by soreness; Soreness peaks 1-3 days after exercise and subsides over 7-10 days

Can be attenuated by subsequent bouts of same type of exercise starting with modest intensity

DOMS is result of eccentric contractions (running down hill, limb extensions against load) causing muscle fiber tearing or damage to Type II fibers (which then causes activation of type IV pain fibers due to inflammation/muscle damage)

(concentric contractions produce less than half muscle damage as in eccentric contractions)

29
Q

Compare/contrast SKM and CM

A

Satellite cells: SKM has them and can regenerate, CM does not

Costameres: SKM has them, CM does not

Getting Ca2+ out of SR: SKM uses EC coupling and CM uses Ca2+-induced Ca2+ release

DHP and RyR: both have them