Physiology of Skeletal Muscle

Physiology of Skeletal Muscle

• Skeletal muscles facilitate body movements through contraction pulling on tendons connected to bones.
• Skeletal muscles maintain body posture.
• Skeletal muscles protect internal organs and support entry/exit points in the body via sphincter muscles.

Characteristics of Muscle Tissue:

• Excitability allows muscles to receive and respond to stimuli.
• Skeletal muscle stimuli involves neurotransmitters from neurons.
• Smooth muscle stimuli can involve neurotransmitters, hormones, stretch, pH, Pco2, or Po2.
• Cardiac muscle stimuli can involve neurotransmitters, hormones, or stretch.
• Contractility allows muscles to shorten when stimulated.
• Contractility is a defining property of muscle tissue.
• Extensibility allows muscles to be stretched.
• Elasticity allows muscles to recoil and resume their original length after being stretched.

Organization of Skeletal Muscle

• Skeletal muscle organs are composed of muscle tissue along with nervous, vascular, and connective tissues.
• The epimysium, a dense irregular connective tissue layer, surrounds the entire muscle. (epi= ?, mysium=muscle)
• Fascicles, or bundles of super-long skeletal muscle cells (muscle fibers), are surrounded by the perimysium, a layer of dense irregular connective tissue (peri=around).
• Endomysium, a fine layer of loose connective tissue, surrounds each muscle cell, which extends the length of the entire muscle organ.
• The epimysium, perimysium, and endomysium are continuous with one another.

Structure of Skeletal Muscle

• Skeletal muscle consists of thousands of parallel muscle cells known as muscle fibers, bundled together.
• Parallel bundles extend between the two ends of the muscle.

Muscle Fiber Structure:

• Each muscle fiber contains an array of myofibrils stacked lengthwise in sarcoplasm.
• Sarcoplasm is the cytoplasm of muscle cells.
• Each muscle fiber has multiple nuclei due to embryonic development through fusion of many cells.
• Alternating dark (A) and light (I) bands create a repeating striated pattern in muscle fibers.
• The myofibril's striations are the reason why the muscle fiber appears striated.

Myofibrils:

• Myofibrils consist of parallel thick and thin myofilaments.
• The organization of myofilaments creates a banding pattern.
• Sarcomere is the the functional unit of repeating pattern.

Sarcomere:

• Sarcomere is the functional unit of the myofibril.
• In the myofibril, thick and thin filaments are arranged to form dark (A bands) and light (I bands).
• H zone bisects the A bands and is lighter than each side.
• M line, made of proteins, connects thick filaments to each other
• Z line bisects the I bands and anchors thin filaments.
• A sarcomere spans from one Z line to the next.
• It is flanked by Z discs. The sarcomere is the area between the Z discs.
• The A band contains a zone of overlap where thick and thin filaments overlap.

Myofilaments:

• Myofilaments are thread-like structures primarily of myosin and actin.

Thick (Myosin) Filaments:

• Thick myofilaments are composed of multiple myosin molecules packed together, each with two globular heads & a long tail.
• The heads protrude and form cross-bridges with thin filaments.
• Each myosin head contains an actin binding site, ATP binding site, and ATPase enzyme.
• Approximately 300 myosin molecules join to form a single thick filament.

Thin (Actin) Filaments:

• Thin filaments are composed of actin, tropomyosin, and troponin.
• Actin is a globular protein that polymerizes into intertwined helical chains.
• Each actin has one active site for myosin cross-bridge binding.
• Tropomyosin strands are located in the grooves present between the two chains of actin. They cover the active site during resting conditions.
• Troponin is a large globular protein with a Calcium binding site. It regulates accessing active sites present on the actin.

Other muscle proteins

• Titin extends from the Z disc to the M line within the thick filament.
• Titin is the largest known protein in the human body with 30,000 amino acids.
• Titin forms the core to hold thick myofilaments in place, keeping the A band organized.
• Titin gives the muscle elasticity.
• Dystrophin is a protein between the sarcolemma and the outermost myofilaments and links actin to an integral membrane protein which in turn links the muscle cell to the endomysium of the entire muscle fiber
• Genetic mutation of the gene coding for dystrophin is one of the root causes of a class of muscle diseases known collectively as muscular dystrophy (MD).
• Duchene muscular dystrophy (DMD), is inherted in a "sex-linked" fashion and affects boys. Most DMD patients become wheelchair bound early in life, usually by age 12 or so. Difficulty breathing usually become problematic by age 20, and is often the cause of their sadly premature death.

Sarcotubular System:

• Transverse (T) Tubules are an extensive network of tubules, surround each myofibril at the junction between I bands, eventually join the plasma membrane, carrying depolarization.
• They contain a voltage sensitive protein called the dihydropyridine (DHP) receptor.
• Sarcoplasmic Reticulum forms sleeve-like segments around each myofibril with enlarged parts known as lateral sacs.
• The modified endoplasmic reticulum stores Calcium. Calcium is released initiating muscle contraction
• Contains Calcium release channel called the ryanodine receptor . Membrane contains Calcium -ATPase which transports Calcium, which keeps the sarcoplasm low during relaxation.

• Transverse Tubules transmit action potential from muscle fibers surface to terminal cisternae of SR to release Calcium.
• Sarcoplasmic Reticulum primary role is to store Calcium keeping its level in cytoplasm very low in relaxed muscle

Receptors

• Nicotinic receptors, DHP receptors, and Ryanodine receptors are the three types of receptors in skeletal muscle needed for contraction.

Muscle Contraction

• Muscle contraction involves filaments sliding past each other which causes a shortening in the sarcomere and muscle fiber.
• Actin and myosin filaments slide past each other during muscle contraction.
• In terms of contraction, the distance between Z discs, the length of the H zone and the length of the I band will shorten.
• Length of the A band remains the same.