Skeletal Muscle Physiology

muscle fiber

myofibrils

thick filaments

myosin

thin filaments

actin

banding

A band

H zone

M line

I band

Z line

sarcomere

transverse tubules at A-I junction

sarcoplasmic reticulum

lateral cisternae

thick filament

actin binding site

myosin ATPase site

thin filament

actin

G actin

F actin

tropomyosin

troponin

binding sites

actin

tropomyosin

Ca²⁺

Molecular basis of skeletal muscle contraction

mechanism of filament sliding during contraction of a myofibril

power stroke

excitation-contraction coupling

synaptic vesicle fusion and neurotransmitter release at the neuromuscular junction

1.	ATP hydrolyzed by ATPase
	ADP & P_i attached to myosin
	energy stored in cross-bridge
2.	Ca²⁺ released at excitation
	actin disinhibited
	actin-myosin binding
3.	Power stroke of cross-bridge
3.	ADP & P_i released
4.	Fresh ATP binds to myosin head
	myosin detaches from actin
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rigor mortis

relaxation

sarcoplasmic reticulum Ca²⁺-pump

contractile activity

latent period: <10 msec

contraction time: ~50 msec

relaxation time ~50 msec

Mechanics of contraction

determinants of whole-muscle tension

twitch

number of fibers contracting

size of muscle

number of motor units recruited

number of muscle fibers per motor unit

tension developed by each contracting fiber

frequency of stimulation

twitch summation

tetanic contraction

length-tension relationship

extent of fatigue

duration of activity

asynchronous recruitment of motor units

type of fiber

oxidative, fatigue-resistant

glycolytic, fatigue-prone

thickness of fiber

hypertrophy

atropy

types of contraction

concentric (isotonic)

muscle actively shortening

eccentric

muscle actively lengthening

isometric

muscle actively held at fixed length

passive stretch

muscle passively lengthening

titin

Muscle metabolism

Energy sources for ATP

existing ATP

creatine phosphate

oxidative phosphorylation: aerobic

glycolysis: anaerobic

muscle fiber types

Characteristic	Slow Oxidative ( Type I )	Fast Oxidative ( Type IIa )	Fast Glycolytic ( Type IIb )	Fast Intermediate
also known as	Slow	Fast, Fatigue Resistant	Fast Fatiguable	Fast Intermediate
myosin heavy chain isoforms	type 1 (cardiac β)	type 2a	types 2b, 2x	type 2a (?)
myosin ATPase activity	low	high	high	high
speed of contraction	slow	fast	fast	fast
resistance to fatigue	high	intermediate to high	low	intermediate
oxidative phosphorylation capacity	high	high	low	intermediate
enzymes for anaerobic glycolysis	low	intermediate to high	high	intermediate
fiber color	red	red	white	red

Muscular Dystrophies

group of inherited muscle-destroying diseases where muscles enlarge due to fat and connective tissue deposits, but muscle fibers atrophy

Duchenne muscular dystrophy (DMD)

inherited, sex-linked disease carried by females and expressed in males (1/3500)

diagnosed between the ages of 2–10

victims become clumsy and fall frequently as their muscles fail

progresses from the extremities upward, and victims die of respiratory failure in their 20s

caused by a lack of the sarcoplasmic protein dystrophin

Becker muscular dystrophy (BMD)

generalized weakness and wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders; calves are often enlarged

similar to Duchenne muscular dystrophy but often much less severe

there can be significant heart involvement

disease progresses slowly and with variability but can affect all voluntary muscles

most with BMD survive well into mid- to late adulthood.

Myasthenia gravis

a relatively rare autoimmune disorder in which antibodies form against acetylcholine (ACh) nicotinic postsynaptic receptors at the myoneural junction

the reduction in the number of ACh receptors results in a characteristic pattern of progressively reduced muscle strength with repeated use of the muscle and recovery of muscle strength following a period of rest

cholinergic nerve conduction to striated muscle is impaired by a mechanical blockage of the binding site by antibodies and, ultimately, by destruction of the binding site

patients become symptomatic once the number of ACh receptors is reduced to approximately 30% of normal

the bulbar muscles are affected most commonly and most severely, but most patients also develop some degree of intermittent generalized weakness

the cholinergic receptors of smooth and cardiac muscle have a different antigenicity than skeletal muscle does; therefore, the disease does not affect them

in the US, the prevalence ranges from 0.5–14.2 per 100,000 people; the prevalence has increased over the past two decades, primarily because of the increased life span of patients with the disease
in the modern era, patients with MG have a near-normal life expectancy
the male-to-female ratio in children and adults is 2:3

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Questions for thought
1.		What is a sarcomere? Describe how its structure allows for the shortening of a skeletal muscle fiber.
2.		Describe the process of excitation-contraction coupling from the release of neurotransmitter by the axon terminal to the disinhibition of the thin filament.
3.		List the four major skeletal muscle fiber types, and, for each, give at least three characteristics that can be used to distinguish it.
4.		Describe the factors which lead to rigor mortis and its resolution.
5.		Compare and contrast Duchenne and Becker muscular dystrophies. Why is myasthenia gravis not considered a muscular dystrophy?
6.		Compare and contrast concentric, eccentric, and isometric contractions. Give use examples for each.
7.		Discuss the factors which contribute to the development of tension within a muscle.

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