Skeletal Muscle Structure and Function

The Triad

• Three structures comprise the triad of a skeletal muscle cell: two terminal cisternae and one transverse tubule.
• The terminal cisternae are enlargements of the sarcoplasmic reticulum, which stores calcium.
• The T-tubule is a deep invagination of the sarcolemma, the cell membrane, which allows action potentials to penetrate into the muscle fiber.

Regulatory Proteins

• Regulatory proteins are responsible for controlling muscle contraction and relaxation.
• In a relaxed myocyte, regulatory proteins are found in the I-band and A-band of the sarcomere.
• The I-band (Isotropic) is the region of the sarcomere that contains only thin filaments (actin).
• The A-band (Anisotropic) is the region of the sarcomere that contains both thin and thick filaments (myosin).

Muscle Structure

• Myofibrils are the basic contractile units of a muscle cell and are made up of repeating units called sarcomeres.
• Z-lines define the boundaries of individual sarcomeres.
• The M-line is the center of the sarcomere and serves as an anchoring point for thick filaments.
• T-tubules run perpendicular to the long axis of the muscle fibers, forming a network that ensures the rapid spread of action potentials.
• Actin and myosin are the two primary contractile proteins.
• Actin comprises the thin filaments, while myosin comprises the thick filaments.

Bare Zone

• The middle of the thick myofilament is called the "bare zone" because it is devoid of myosin heads, also known as cross-bridges.
• This region is responsible for the attachment of the thick filaments to the M-line.

Titin

• Titin is a structural protein that extends along each thick filament from the M-line to the Z-line.
• It functions as a molecular spring, providing elasticity to the muscle fiber and preventing overstretching.

Calcium Storage and Release

• The sarcoplasmic reticulum (SR) is a network of membrane-enclosed tubules that surrounds each myofibril.
• The SR stores calcium ions.
• T-tubules transmit action potentials from the sarcolemma to the SR.
• The arrival of an action potential at the T-tubule triggers the release of calcium ions from the SR.

Myosin

• Myosin is a motor protein that converts chemical energy (ATP) into mechanical energy to drive muscle contraction.
• In its energized state (bound to ADP and Pi), myosin has a high affinity for actin.
• The binding of ATP to myosin results in a power stroke, causing the thin filaments to slide past the thick filaments.

Excitation-Contraction Coupling

• This refers to the series of events that link an action potential at the neuromuscular junction to the activation of cross-bridge cycling.
• The process begins with the release of acetylcholine from the motor neuron at the neuromuscular junction.
• Acetylcholine binds to receptors on the muscle fiber membrane, triggering an action potential that spreads along the sarcolemma and into the T-tubules.

Intracellular Calcium Regulation

• At rest, calcium is stored within the SR, maintaining a low concentration in the cytosol.
• When an action potential reaches the SR, calcium is released from the SR into the cytosol.
• This influx of calcium binds to troponin, causing a conformational change that exposes the myosin binding sites on actin.
• After contraction, calcium is actively pumped back into the SR via the calcium ATPase pump, restoring the muscle to a relaxed state.

Troponin

• Troponin, a regulatory protein, binds to calcium ions.
• This binding triggers a conformational change that moves tropomyosin away from the myosin binding sites on actin, allowing contraction to occur.

Sliding Filament Mechanism

• Muscle contraction occurs as the thin filaments slide past the thick filaments.
• The length of the thin and thick filaments themselves does not change during contraction.
• The Z-lines move closer together, shortening the sarcomere.
• The H-zone, which is the region of the sarcomere containing only thick filaments, also shortens.
• The I-band, which is the region of the sarcomere containing only thin filaments, also shortens.

Muscle Fatigue

• Muscle fatigue is a physiological state where the muscle can no longer maintain its force of contraction.
• Several factors can contribute to muscle fatigue, including:
  • Depletion of ATP
  • Accumulation of lactic acid
  • Depletion of glycogen stores
  • Changes in the concentration of ions (e.g., Ca2+, K+)