Muscle Physio 2

Excitation-Contraction Coupling

Excitation-contraction coupling is the process by which a muscle action potential leads to muscle contraction. Motor neurons innervate skeletal muscle cells and divide into terminal branches, each forming a neuromuscular junction with a muscle cell. This process is similar to chemical synapses.

Neuromuscular Junction

  1. Action Potential Arrival: An action potential depolarizes the motor neuron's axon terminal.
  2. Calcium Influx: Depolarization opens voltage-gated calcium channels, causing an influx of calcium ions into the motor neuron.
  3. Exocytosis: The calcium influx triggers the exocytosis of synaptic vesicles containing acetylcholine (ACh).
  4. Acetylcholine Release: Acetylcholine is released into the synapse and diffuses across to the muscle cell membrane.
  5. Receptor Binding: Acetylcholine binds to chemically-gated ion channel receptors on the muscle cell membrane, opening them.
  6. End Plate Potential (EPP): The opening of these channels leads to membrane depolarization, known as the end plate potential.
  7. Action Potential Initiation: The EPP opens voltage-gated sodium channels in adjacent membrane regions, initiating an action potential that propagates throughout the muscle cell.
  • A single EPP is sufficient to trigger an action potential in the muscle cell.

T-Tubules

  • T-tubules are extensions of the plasma membrane that extend into the muscle fiber.
  • Function: They propagate the action potential from the surface of the muscle fiber to its interior.

Sarcoplasmic Reticulum

  • The sarcoplasmic reticulum is a modified endoplasmic reticulum that surrounds myofibrils.
  • Calcium Storage: It stores calcium ions (Ca^{2+}).
  • Proximity to T-Tubules: Segments of the sarcoplasmic reticulum form sacs in close contact with the T-tubules.
  • Calcium Release: When an action potential reaches the T-tubules, it triggers the release of calcium from the sarcoplasmic reticulum into the cytoplasm.

Calcium Release Mechanism

  1. Foot Proteins (Calcium Ion Channels): Located in the sarcoplasmic reticulum; high Ca^{2+} concentration inside the sarcoplasmic reticulum and low concentration in the cytoplasm, facilitating Ca^{2+} ion flow into cytoplasm when opened.
  2. Dihydropyridine Receptors (DHPR): Voltage sensors on the T-tubules that attach to foot proteins. When an action potential is propagated along the T-tubule, these receptors sense the change in membrane potential.
  3. Coupling: The activated DHPR triggers the opening of calcium channels (foot proteins) on the sarcoplasmic reticulum, releasing calcium into the cytoplasm.

Role of ATP in Muscle Contraction

  • Muscle contraction requires ATP.
  • Myosin has an ATPase site, meaning it can break down ATP.
  1. ATP Binding: ATP binds to myosin.
  2. ATP Hydrolysis: ATP is hydrolyzed into ADP and inorganic phosphate (Pi), and energy is stored in the myosin molecule in the form of a shape change.
  3. Attachment: When calcium is available, energized myosin heads attach to the thin filaments.
  4. Power Stroke: Energy stored in the myosin head is released, causing the power stroke.
  5. Release of ADP and Pi: After the power stroke, ADP and Pi are released.
  6. Crossbridge Formation: The actin and myosin remain bound until a new ATP molecule binds, breaking the crossbridge.
  7. Cycle Continues: As long as calcium is present, this cycle continues.
  • In the absence of ATP, crossbridges do not break, leading to rigor mortis after death. After death, calcium concentration rises, preventing inhibition by tropomyosin, so myosin can attach to the thin filament, being already energized, but cannot detach without new ATP.

Termination of Muscle Contraction

  1. Calcium Pump: A calcium pump in the sarcoplasmic reticulum actively transports calcium from the cytoplasm back into the sarcoplasmic reticulum.
  2. Calcium-Binding Proteins: Calcium-binding proteins in the sarcoplasmic reticulum help to soak up calcium.
  3. Cessation of Action Potential: When action potentials cease, calcium is no longer released.
  4. Calcium Removal: The calcium pump removes cytoplasmic calcium, terminating the contraction.

Contraction of Whole Muscles

  • Whole muscles contract in a graded fashion.

Control of Contraction Force

  1. Number of Muscle Fibers: The number of muscle fibers that contract can vary.
  2. Motor Units: A motor neuron and all the muscle fibers it innervates form a motor unit.
  3. Motor Unit Recruitment: During a weak contraction, few motor units are activated; during a forceful contraction, many motor units are activated.
  • Muscles for fine, precise movements have small motor units (few dozen muscle fibers per axon), while muscles for powerful contractions (e.g., leg muscles) have large motor units (thousands of muscle fibers per motor neuron).

Tension Developed by Each Muscle Fiber

  1. Stimulation Frequency: The frequency of action potentials affects tension.
  2. Twitch: A single action potential produces a weak contraction called a twitch.
  3. Summation: If a muscle doesn't completely relax before the next action potential, the twitches summate.
  4. Tetanus: Rapid stimulation results in a smooth, sustained contraction where the muscle fiber does not relax at all.
  • The duration of an action potential (1-2 milliseconds) is much shorter than the duration of a muscle twitch (100 milliseconds).

Length-Tension Relationship

  • The maximal tension depends on the length of the muscle at the start of contraction.
  • L0 (L naught) is the optimal length where maximal tension is generated. At this length, the overlap of thick and thin filaments is optimal.
  • Muscles cannot vary beyond 30% of L0 due to their attachment.

Types of Contractions

  1. Isotonic Contraction: Muscle tension is constant, and the muscle changes length (e.g., lifting an object).
  2. Isometric Contraction: Muscle length is constant, and tension develops without shortening (e.g., trying to lift an object that is too heavy).

Energy Sources for Muscle Contraction

  • ATP is required for the power stroke, detachment of myosin from actin, and reuptake of calcium into the sarcoplasmic reticulum.

ATP Sources

  1. Phosphagens: High-energy phosphate groups transferred to ADP to form ATP.
  2. Oxidative Phosphorylation
  3. Glycolysis

Creatine Phosphate

  • Creatine phosphate is in higher concentration in muscle than ATP.
  • Creatine Kinase: The enzyme that transfers a high-energy phosphate from creatine phosphate to ADP.

Anaerobic Metabolism

  • Low oxygen supply leads to anaerobic metabolism, producing lactic acid and leading to acidosis and muscle fatigue.

Aerobic Metabolism

  • Adequate oxygen supply allows for aerobic metabolism, which produces large amounts of ATP but is slower.

Oxygen Debt

  • At the end of muscle activity, creatine phosphate and glycogen levels are restored by energy-dependent processes.
  • This results in an elevated level of oxygen consumption (oxygen debt) even after exercise.

Types of Muscle Fibers

  • Muscle fibers differ based on contraction speed and ATP source.

Fast Twitch vs. Slow Twitch

  • Fast Twitch: Myosin heads split about 600 ATP molecules per second.
  • Slow Twitch: Myosin works about half as fast (~300 ATP molecules per second).

Oxidative vs. Glycolytic Fibers

  1. Slow Oxidative Fibers: Rich in mitochondria and myoglobin, small diameter, well-supplied with capillaries, red in color, slow to fatigue.
  2. Fast Glycolytic Fibers: Fewer mitochondria, larger, little myoglobin, not well-supplied with capillaries, white in color, rich in glycogen, fatigue rapidly.
  3. Fast Oxidative Fibers: Intermediate characteristics with fast myosin, many mitochondria, and slow to fatigue.
  • Most muscles contain a mixture of fiber types.

Muscle Fiber Examples (Fish)

  • Slow Red Muscle: 10-25% of trunk muscle, used for steady cruising.
  • White Fast Muscle: Most of the trunk muscle mass, used for bursts of speed, fatigues quickly (used for avoiding predators or capturing prey).