Skeletal Muscle

A muscle is an excitable tissue having ability to contract. There are three types of muscles:

1) Skeletal muscle

2) Smooth muscle

3) Cardiac muscle

Skeletal Muscle

►Striated appearance

►Under voluntary control

►Innervated by somatic motor nerve

►About 40 % of body weight

A muscle fiber or simply a muscle cell consists of:

►Sarcolemma

►‘T’ tubules

►Sarcoplasm

►Sarcoplasmic reticulum

►Mitochondria

►Myofibrils

►Myofilaments

Actin

►Thin filaments -double the number, half the diameter

Myosin

►Thick filaments -half the number, double the diameter

Special arrangement of actin and myosin filaments give striated appearance to skeletal muscle.

‘I’ bands (less dense)

►Contain actin only with ‘Z’ line in center

‘A’ bands (more dense)

►Contain both actin and myosin

‘H’ zone

►Central zone occupied by myosin only

‘M’ line

►unites myosin filaments with each other

►Binds with titin protein and anchors myosin

Actin filament:

Composed of three proteins

►Actin

Contain active sites

►Tropomyosin

Covers active sites

►Troponin (I, C, T)

Binds tropomyosin to actin

Myosin filament

Composed of myosin molecules

►Two heavy and four light chains

►Tails of molecules form body of filament

►Heads form cross bridges

Sarcomere

►Structural and functional unit of muscle fiber

►Lies between 2 successive ‘Z’ lines

Sarcomere -resting length = 2.2 μm

►Maximum overlap of myosin heads with actin

►Length of myosin filament = 1.6 μm

►Length of actin filament = 1μm

Skeletal muscle contraction

Sliding filament mechanism walk along theory)

►Process by which sarcomere shortens and contraction takes place

►Pulling inwards of actin filaments

►Myosin heads bind with active site of actin

►Power stroke occurs and actin filaments slide inwards over myosin filaments

General mechanism

►Generation of action potential in muscle fiber

►Spread of action potential along sarcolemma and deep in the cell through ‘T’ tubules

►Release of Ca++ions from sarcoplasmic reticulum

►Uncovering of active sites of actin

►Binding of myosin heads to actin

►Contraction by sliding filament mechanism

Molecular mechanism

►Actin & myosin love story

►Role of tropomyosin as villain

►Role of Ca++in the love story

►Energization of myosin head by cleaving ATP

►ADP and Pi remain attached

►Release of Ca++from sarcoplasmic cistern

►Binding of Ca++with Troponin C

►Uncovering of active sites of actin

►Binding of myosin heads with actin

►Power stroke

►Bending of cross bridge and inward movement of actin

►Detachment of ADP from myosin heads

►Binding of new ATP with myosin head

►Detachment of myosin heads from actin

►Myosin head energized by cleaving ATP into ADP and Pi & ready for new cycle

Relaxation

►When cytosolic Ca++decreases

►Pumping of Ca++back into sarcoplasmic reticulum

►Role of Ca++pump located at sarcoplasmic reticular membrane

►Energy consuming process -requires ATP

►Release of Ca++from troponin C

►Blocking of active sites of actin

During contraction

►One end of muscle remain fixed, other end shortens

►Centre of sarcomere slides towards fixed end

Utilization of ATP

►Energization of myosin head

►Detachment of myosin heads from actin

►Removal of Ca++from cytosol

Sources of energy for muscle contraction

►Continuous supply of ATP is essential

►Creatine phosphate

►Oxidative phosphorylatoin

►glycolysis

Rigor mortis

►Contracture of muscles after death

►Cause

►Non availability of ATP

►Cytosolic Ca++rises (failure of Ca++pump)

►Myosin heads can not detach from actin

►Subsides after several hours/days

►Due to destruction of contractile proteins

Excitation contraction coupling

►Series of events by which muscle excitation leads to its contraction

►Propagation of action potential from sarcolemma into ‘T’ tubules

►Activation of dihydropyridine (DHP) receptors

►Opening of ryanodine channel and Ca++influx

►Binding of Ca++with troponin C

►Uncovering of active sites of actin

►Binding of myosin heads with actin

►Contraction by sliding filament mechanism

Release of Ca++from sarcoplasmic cistern couples excitation with contraction

Length tension relationship

Tension generated during contraction depends upon initial sarcomere length

Resting length

►Sarcomere length 2 to 2.2 μm

Maximum myosin & actin overlap is possible

►Maximum tension is produced

Sarcomere length > or < than resting length

Actin & myosin overlap not optimal

►Less tension produced

Tension generated during contraction

►Depends upon number of myosin heads bound to actin

►If actin slides inwards

►Sarcomere (or the whole muscle) shortens

►If actin can not slide

►Sarcomere (or the whole muscle) length remains the same

Tension

►Force exerted by a contracting muscle on an object

Load

►Force exerted by the object on muscle

Tension & load are opposing forces

Whether muscle fiber will shorten during contraction or remain the same depends upon relative magnitudes of tension and load

Isometric contraction

►Tension during contraction increases but length of muscle remains the same

►Load > tension

►Trying to lift heavy loads (but not actually lifting up)

Isotonic contraction

►Tension during contraction remains the same but muscle length changes

1) Concentric isotonic contraction

►Load < tension

►Muscle shortens during contraction

►Lifting a weight up running, walking etc

2) Eccentric isotonic contraction

►Load > tension

►Already contracted muscle lengthens

►Lowering a weight to ground

Simple muscle twitch

►Mechanical response of a single muscle fiber to a single action potential

►Latent period (10 ms)

►Contraction period (40 ms)

►Relaxation period (50 ms)

►Total duration -100 ms (varies)

►Doesn’t have refractory period

Motor unit

►A motor neuron and all the muscle fibers it innervates constitutes a motor unit

►Motor unit recruitment

►Activation of more & more motor units

►Initially smaller than larger units (size principle)

►Asynchronous recruitment

►Alternating motor unit activity

►Delays fatigue

►Provides smooth contraction even at low frequency

Summation

►Adding together of individual twitch contractions to increase the intensity of overall muscle contraction

1) Multiple fiber summation

2) Frequency summation

Multiple fiber summation

►More the fibers (motor units) taking part in contraction more will be the force of contraction

►For weak contraction, smaller and fewer motor units are stimulated

►For stronger contractions more & more motor units are stimulated (recruitment)

Frequency summation, tetanus or tetanization

►Sustained contraction due to repeated stimuli of high frequency

►Incomplete tetanization

►Complete tetanization

Incomplete tetanization

►Muscle fiber is stimulated at such a frequency that every next stimulus falls during previous relaxation period

►Subsequent contraction is superimposed on the previous relaxation

►Force of subsequent contractions rises due to beneficial effect of Ca++

►Muscle fiber partially relaxes between stimuli

Complete tetanization

►Muscle fiber is stimulated at such a frequency that every next stimulus falls during previous contraction period

►Subsequent contractions merge with the previous ones

►Smooth contraction of greater force is achieved

►No relaxation phase

►Leads to fatigue

Muscle fatigue

►Decrease in muscular activity due to repeated stimuli

Causes

a.In muscle

►Lack of nutrients and glycogen

►Lack of oxygen

►Accumulation of lactic acid

►Conduction failure along ‘T’ tubules -blockage of Ca++release for sarcoplasmic cistern

b. In Neuromuscular junction

►Depletion of Acetyl choline

3. In CNS

►CNS cannot send excitatory signals to the contracting muscles

►Generally psychological

►Fatigue reverses by taking rest

Muscle fiber types

►On the basis of contraction velocity

1) Slow

2) Fast

►On the basis of formation of ATP

1) Oxidative

2) Glycolysis

Three types

►Slow oxidative fibers

►Low myosin ATPase activity

►High oxidative capacity

►Fast oxidative fibers

►High myosin ATPase activity

►High oxidative capacity

►Intermediate glycolytic capacity

►Fast glycolytic fibers

►High myosin ATPase activity

►High glycolytic capacity

Muscle tone

►Tautness in muscle when at rest

►Due to continuous firing of some motor neurons

►Contraction of some motor units

►Alternating pattern of motor units contraction

Remodeling of muscle

►Muscle remodels to match its function

Hypertrophy

►Increase in total mass of muscle

►Occurs in strength exercise (anaerobic exercise) -weight lifting

►Increase in fiber size

►Increase number of actin and myosin

►Change in metabolic machinery

Atrophy

►Decrease in total mass of muscle

►Denervation atrophy

►Abolishment of trophic signals

►Disuse atrophy

►When muscle is not used for long time

Clinical physiology

►Hypocalcemic tetany

►↓ ECF Ca++→ ↑ Na+permeability

►Spontaneous contractions

►Muscle cramps

►Involuntary tetanic contractions due to abnormally high rates of action potentials

►due to over-exercise

►Dehydration

►Electrolyte imbalance