Skeletal Muscle Structure and Function

Muscle Contractile Responses

• Excitation-contraction coupling: the mechanism by which an action potential causes muscle fiber contraction.

Skeletal Muscle

• Each muscle fiber is a single unit, multinucleated, and contains myofibrils.
• Myofibrils are surrounded by the sarcolemma.
• The sarcolemma forms deep invaginations called transverse tubules (T tubules) within myofibrils.
• Each myofibril contains interdigitating thick and thin filaments arranged longitudinally and cross-sectionally in sarcomeres.

Skeletal Muscle Microstructure

• Sarcolemma: plasma membrane of the muscle fiber.
• Myofibrils: threadlike strands within muscle fibers.
  • Actin (thin filament): contains troponin and tropomyosin.
  • Myosin (thick filaments): involved in muscle contraction.
• Sarcoplasm: cytoplasm of the muscle fiber.
• Sarcoplasmic reticulum: storage sites for calcium, surrounding myofibrils.
• Transverse tubules: invaginations of the sarcolemma that allow the action potential to travel deep into the muscle fiber.

The Sliding Filament Theory

• The most widely accepted theory explaining muscle fiber contraction.
• Myosin filaments use energy from ATP to "walk" along actin filaments with their cross-bridges.
• This pulls the actin filaments closer together, causing muscle contraction.

Sequence of Steps Leading to Muscle Contraction

• An action potential travels along a motor nerve to its terminal end.
• The nerve releases acetylcholine (ACh) at the terminal end.
• ACh binds to receptors on the muscle fiber membrane, opening cation channels.
• Sodium ions (Na⁺) flow into the muscle fiber, causing local depolarization.
• This depolarization opens voltage-gated Na⁺ channels, initiating an action potential that spreads throughout the fiber and into the T-tubules.

How Depolarisation in the T-tubule Membrane Opens Ca²⁺ Channels on the Sarcoplasmic Reticulum (SR) Membrane?

• Dihydropyridine Receptor (DHPR): a voltage sensor located in the T-tubule, closely associated with the foot of the sarcoplasmic reticulum.
• Ryanodine Receptor (RyR): a receptor located in the membranes of SR terminal cisternae, triggered by the impulse from DHPR.
• The impulse causes RyRs to open and release Ca²⁺ into the intracellular space of the muscle fiber.

The Contraction Sequence

• Free Ca²⁺ binds to troponin C, a protein component on the actin filaments.
• The troponin complex (troponin T, troponin I, troponin C) undergoes conformational change, moving the tropomyosin molecule.
• This uncovers the myosin-binding sites on the actin filaments.
• Myosin heads bind to the actin filament, releasing ADP+Pi and initiating the power stroke.
• This results in shortening of the sarcomere.

Relaxation of the Muscle Fiber After Contraction

• ATP binds to myosin heads, releasing them from actin.
• Ca²⁺ is reaccumulated in the sarcoplasmic reticulum by the sarcoendoplasmic reticulum Ca²⁺ ATPase (SERCA) pump.

Rigor Mortis

• After death, muscles contract and become rigid due to a lack of ATP needed to detach the cross-bridges from the actin filaments.
• This rigidity lasts until muscle proteins deteriorate, approximately 15-25 hours after death.
• The process is faster at higher temperatures.

Characteristics of Whole Muscle Contraction

• Length-Tension Relationship: the amount of tension generated depends on the length of the muscle before stimulation.
  • Overly contracted: thick filaments are too close to Z discs and can't slide, resulting in weak contraction.
  • Too stretched: little overlap between thin and thick filaments, limiting the formation of cross bridges and causing weak contraction.
  • Optimal resting length: produces the greatest force when the muscle contracts.
• Muscle tone: continuous and passive partial contraction of muscles during resting state.

Effect of Muscle Length on the Force of Contraction

• Active tension decreases as the muscle is stretched beyond its normal length.

Relationship of Contraction Velocity to the Load

• As the load increases, the velocity of contraction decreases.
• When the load equals the maximum force the muscle can exert, the velocity of contraction becomes zero, and no contraction occurs.

Types of Muscle Contraction

• Isometric: muscle does not shorten during contraction but develops maximal tension (e.g. gripping).
• Isotonic: muscle shortens while the tension remains constant throughout the contraction (e.g. lifting a load).

Force Summation

• Adding together individual twitch contractions to increase the intensity of overall muscle contraction.
• Multiple fiber summation: increasing the number of motor unit contractions.
• Frequency summation: increasing the frequency of contractions.

Motor Unit

• All muscle fibers innervated by a single nerve fiber.

Mechanism of Tetanus

• Continuous stimulation of the muscle results in sustained contraction called tetanus.
• The intracellular Ca²⁺ concentration remains high, leading to continuous binding of Ca²⁺ to troponin C and continuous cross-bridge cycling.

Muscle Fatigue

• Prolonged and strong muscle contraction leads to muscle fatigue.
• Muscle fatigue is directly proportional to the rate of depletion of muscle glycogen.
• It results in:
  • Failure of contractile and metabolic processes to sustain work output.
  • Diminished transmission of nerve signals through the neuromuscular junction.
  • Interruption of blood flow, leading to loss of nutrient supply and oxygen.
  • Fatigue diminishes muscle contraction.