Physiology of Skeletal Muscles

Muscle tissue shortens and develops tension leading to movement
There are two main types of muscle: striated muscles (skeletal and cardiac) and smooth muscles

Skeletal muscles make up 40% of the body and are responsible for moving the body
Each muscle fiber is a single cell with multiple nuclei, sarcolemma, and many parallel myofibrils
Each myofibril contains thick filaments (myosin) and thin filaments (actin)

The sarcomere is the functional unit of the muscle
It extends between two transverse protein sheets called Z lines
The sarcomere contains thick filaments (myosin) in the middle and thin filaments (actin) arranged on both sides with one end attached to the Z line

The sarco-tubular system consists of T-tubules and the sarcoplasmic reticulum (SR)
T-tubules are invaginations of the muscle fiber membrane that transmit action potential from the surface to inside the fiber
The SR is a site of storage of Ca2+ and extends longitudinally between the T-tubules

Each myosin molecule is made up of 2 heavy chains and 4 light chains
The two heavy chains form a helix, and their terminal portions with the 4 light chains form 2 arms and globular heads called cross bridges
The myosin head contains actin binding site, ATP binding site, and ATPase activity that hydrolyses ATP

Thin filaments consist of three muscle proteins: actin, tropomyosin, and troponin
Actin molecules are arranged in a double helix and have active sites that can bind with myosin cross bridges
Tropomyosin molecules form strands that cover active sites on actin molecules during rest
Troponin is a globular protein that attaches tropomyosin strands to actin and has affinity to actin, tropomyosin, and Ca2+

Neuromuscular transmission is the transmission of action potential from alpha motor nerve to the muscle along the neuromuscular junction
The neuromuscular junction is the area between the ending of the motor nerve and the skeletal muscle fiber
The motor nerve releases acetylcholine, which binds to its receptors on the motor end plate, leading to an increase in the permeability of the muscle fiber membrane to Na+ and depolarization

Arrival of action potential: action potential reaches the ending of the motor nerve, causing Ca2+ to enter the nerve endings and release of acetylcholine
Postsynaptic response: acetylcholine diffuses and binds to its receptors on the motor end plate, leading to an increase in the permeability of the muscle fiber membrane to Na+
End plate potential: the depolarization of the muscle fiber membrane leads to an end plate potential, which is a graded, non-propagated response
Acetylcholine degradation: acetylcholine is hydrolyzed by choline esterase in the synaptic cleft

Drugs that stimulate neuromuscular transmission: drugs that have acetylcholine-like actions or inactivate choline esterase
Drugs that block neuromuscular transmission: drugs that compete with acetylcholine for its receptors on the motor end plate

Electric changes: the electrical events in skeletal muscle are like those in nerve, with a resting membrane potential of about -90mV and an action potential that precedes contraction by about 2 msec
Mechanical changes: excitation-contraction coupling is the mechanism by which action potential in the muscle initiates muscle contraction

Release of Ca2+: action potential opens Ca2+ release channels on the SR, leading to rapid Ca2+ release and binding to troponin
Activation of proteins: troponin undergoes conformational changes, causing tropomyosin to move away from its position covering the binding sites on actin
Generation of tension: the heads of the bridges of myosin combine with the binding sites on actin, and contraction begins through cross-bridge cycling
Relaxation: Ca2+ is removed from the cytoplasm by the Ca2+ pump on the SR, and troponin returns to its original state, stopping cross-bridge cycling