Muscle Biology Fundamentals

Muscle Physiology Overview

• Muscle tissue constitutes 50% of the body weight.
• Muscle cells are specialized for converting chemical energy (ATP) into mechanical energy.
• Several types of muscle exist, each adapted for specific functions (e.g., locomotion, blood pumping, peristalsis).

Muscular System Functions

• Body movement.
• Maintenance of posture.
• Respiration.
• Production of body heat.
• Communication (speech, writing, expression).
• Constricting organs and vessels.
• Heart beat.

Properties of Muscle

• Contractility: Ability to shorten with force.
• Excitability: Ability to respond to a stimulus.
• Extensibility: Ability to be stretched.
• Elasticity: Ability to recoil to original resting length after stretching.

Muscle Tissue Types

• Skeletal Muscle:
  • Attached to bones.
  • Multinucleated and striated.
  • Voluntary control (conscious action) and involuntary control (reflexes).
• Cardiac Muscle:
  • Found only in the heart.
  • Striated, but branching pattern and intercalated discs.
  • Involuntary and automatic.
  • Usually single nucleus.
• Smooth Muscle:
  • Found in walls of hollow organs, blood vessels, etc.
  • Non-striated.
  • Involuntary.
  • Single nucleus.

Skeletal Muscle (Striated Muscle)

• Attaches to the skeleton.

• Microscopically displays striations.

• Is voluntary, controlled consciously.

• Multinucleated cells.

• Cells have diameters between 10 and 100 μm and lengths extending up to 25 cm.

Skeletal Muscle Fibers Repair

• Skeletal muscle fibers damaged after birth cannot be replaced by the division of existing muscle fibers.
• However, new fibers can be formed from undifferentiated satellite cells.
• Satellite cells are located adjacent to the muscle fibers and differentiate similar to embryonic myoblasts.

Skeletal Muscle: Nerve and Blood Supply

• Each muscle is typically served by a nerve, an artery, and one or more veins.
• Nerves, arteries, and veins enter near the central part of the muscle and branch throughout it.
• Each muscle fiber (cell) is supplied with a nerve ending that controls contraction.
• Contracting fibers require a continuous supply of oxygen and nutrients via arteries.
• Muscle cells produce metabolic wastes that are removed via veins.

Skeletal Muscle – CT Sheaths

• Skeletal muscles are surrounded by three connective tissue sheaths.
• Endomysium: Delicate connective tissue surrounding each muscle fiber (cell).
• Perimysium: Connective tissue surrounding groups of muscle fibers.
• Epimysium: Dense regular connective tissue surrounding the entire muscle.
• Tendon or aponeurosis formation at the end of the muscle is formed by the collagen fibers of these 3 sheaths uniting.
• They provide support, strength, flexibility, and electrical insulation.

Microscopic Anatomy – Skeletal Muscle Fiber

• Sarcoplasm: Muscle cell cytoplasm.
• Sarcolemma: Muscle cell membrane.
• Within the muscle fiber (cell), there are also myofibrils, sarcoplasmic reticulum, and T-tubules.
• Sarcoplasm contains glycosomes (granules of glycogen) and myoglobin (oxygen-binding protein).

Myofibrils and Striations

• Each muscle fiber is made from many myofibrils containing the contractile elements of skeletal muscle cells.
• Myofibrils compose about 80% of the muscle volume.
• Myofibrils are made up of myofilaments (thick and thin).

Myofilaments: Thick and Thin

• Thick filaments: Composed of myosin protein.
• Thin filaments: Composed of actin protein, and regulatory proteins tropomyosin and troponin.
• Myosin consists of two heads and one tail.
• Actin is a major component of the thin filament; there are myosin binding sites on actin in the thin filament.
• Tropomyosin molecules are long filaments that spiral around actin and block active sites in a relaxed muscle fiber.
• Troponin molecules bind to tropomyosin and actin, and bind calcium ions, triggering contraction.
• A band in myofibrils/muscle contains the thick filaments, and is made up of parts of thick and thin filaments.

### Structure of Actin and Myosin

• Describe the structure of actin and myosin filaments, including their components (heavy and light chains, hinge regions, etc.), and their role in sarcomere structure.

Myofibrils - Striations - Banding

• The arrangement of myofibrils creates a repeating series of dark (A bands) and light (I bands) bands.
• Each segment is a sarcomere, the smallest functional contractile unit of a muscle.
• Specific regions within a sarcomere include the Z line (or disc), H zone or band, and M line.
• There are thick filaments in the A band, and thick and thin filaments in both the A and I bands.

Sarcomere Shortening

• Actin filaments move towards the center of the sarcomere.
• The sarcomere shortens when the Z disks move closer together.
• A and I bands change in appearance as the muscle contracts and shortens.

Ca2+ and the Contraction Mechanism

• Calcium ions and regulatory proteins (troponin, tropomyosin) are essential for muscle contraction.
• At low intracellular calcium levels, tropomyosin blocks the binding sites of actin, and myosin cannot bind.
• Increasing intracellular calcium causes a conformational change in troponin, causing tropomyosin to move away from the actin binding sites, allowing the myosin head to attach and detach and initiating the power stroke cycle.

Neuromuscular Junction

• Junction where the motor neuron stimulates the muscle fiber.
• The axon of the motor neuron branches into several terminals forming the presynaptic part of the neuromuscular junction.
• The postsynaptic part of the junction is the muscle cell membrane, with folds containing nicotinic ACh receptors.
• The pre- and postsynaptic membranes are separated by the synaptic cleft, containing acetylcholinesterase (AChE).

Electrical Events at the Neuromuscular Junction

• Depolarization of the nerve terminal causes the release of acetylcholine (ACh) into the synaptic cleft.
• ACh binds to receptors on the muscle fiber, leading to depolarization (end-plate potential).
• Depolarization triggers an action potential in the muscle fiber, initiating muscle contraction.

Propagation of Action Potential on Muscle Membrane

• The action potential spreads through the T tubules.
• This stimulates the release of calcium ions from the SR, causing muscle contraction through the cross-bridge cycle.

Dihydropyridine and Ryanodine Receptors

• Action potentials in T-tubules activate DHP receptors, causing the release of calcium ions from the sarcoplasmic reticulum terminal cisternae.
• Calcium ions initiate muscle contraction.

Neuromuscular Transmission (Toxins and Drugs)

• Presynaptic blockade (e.g., Botulinum toxin) interferes with ACh release.
• Postsynaptic blockade (e.g., Curare-Tubocurarine) prevents ACh from binding and triggering a muscle contraction.

Sliding Filament Model of Contraction

• The sliding filament model explains how muscle fibers shorten during contraction.
• Myosin heads bind to actin filaments, causing them to slide past each other.
• The cross bridge cycle describes the individual steps involved in the overlapping, sliding filament mechanism of the contraction process.