Muscle Tissue and Skeletal Muscle Contraction

General Characteristics and Types of Muscular Tissue

  • General Capability: All muscles possess the ability to contract or shorten. This action results in the movement of the body or the movement of substances within the body.

  • Muscle Tissue Types:

    • Skeletal Muscle:

      • Appearance: Striated (striped), cylindrical, and multinucleated. Nuclei are located eccentrically (at the periphery).

      • Organization: Fibers are arranged in parallel.

      • Location: Attached to the skeleton or the skin.

      • Control: Voluntary.

      • Stretch Capacity: Low compared to other types.

    • Cardiac Muscle:

      • Appearance: Striated, cylindrical, and branched. Contain one or two central nuclei. Notable for having intercalated disks (junctions between cells).

      • Location: Walls of the heart.

      • Control: Involuntary.

      • Stretch Capacity: Moderate stretch.

    • Smooth Muscle (Visceral Muscle):

      • Appearance: Spindle-shaped with a single central nucleus. No striations are present.

      • Location: Walls of hollow organs, including the stomach, intestines, urinary bladder, uterus, and blood vessels. Also found in the eye and associated with hairs (arrector pili).

      • Control: Involuntary.

      • Stretch Capacity: Extreme stretch.

Functional Characteristics and Functions of Muscle

  • General Functional Characteristics:

    • Contractility: The ability of a muscle to shorten with significant force.

    • Excitability: The capacity of a muscle to respond to a specific stimulus, which may be provided by a nerve or a hormone.

    • Extensibility: The property where a muscle can be stretched back to its normal resting length and even beyond to a limited degree.

    • Elasticity: The ability of a muscle to recoil to its original resting length after being stretched.

  • General Muscle Functions:

    • Motion: Contraction moves bones for body movement, moves blood through vessels, facilitates peristalsis (squeezing of the intestines), and powers the contraction of the gall and urinary bladders.

    • Posture Maintenance / Joint Stabilization: Constant tension helps support the body to remain upright and stabilizes skeletal joints.

    • Thermoregulation: Muscle contraction results in the release of heat energy, helping to maintain a constant body temperature.

    • Protection: Helps protect bones and internal organs.

    • Fluid Movement: The pressure generated by contractions assists the movement of fluids within the cardiovascular and lymphatic systems.

Structure and Organization of Skeletal Muscle

  • The Muscle as an Organ: A skeletal muscle is considered an organ because it is composed of several tissues working together, primarily connective tissue (the framework) and muscle tissue (the contractile element).

  • Connective Tissue Coverings:

    • Epimysium: Connective tissue that surrounds the entire muscle. It becomes part of the fascia, and its collagen fibers extend to form tendons that attach to bones.

    • Perimysium: Connective tissue that surrounds bundles of muscle fibers known as fascicles.

    • Endomysium: Connective tissue that surrounds individual muscle fibers (cells).

  • Microscopic Anatomy of a Muscle Fiber:

    • Sarcolemma: The plasma membrane of the muscle fiber.

    • Sarcoplasm: The cytoplasm of the muscle fiber.

    • Sarcoplasmic Reticulum (SR): A specialized endoplasmic reticulum that serves as a calcium storage site. It includes terminal cisternae located near T-tubules.

    • T-tubules (Transverse Tubules): Invaginations of the sarcolemma that allow electrical impulses to reach the interior of the fiber.

    • Triad: A structure formed by one T-tubule and two adjacent terminal cisternae.

    • Myofibrils: Long, cylindrical structures within the fiber composed of myofilaments (thin and thick filaments).

    • Mitochondria: Provide the necessary ATP for contraction.

    • Satellite Cells: Cells associated with the fiber that participate in repair.

    • Development: Skeletal muscle fibers form through the fusion of multiple myoblasts, which explains their multinucleated nature.

The Sarcomere and Myofilaments

  • Sarcomere Structure: The functional unit of a myofibril, extending from one Z disc (Z line) to the next.

    • Z disc: Boundaries of the sarcomere; they anchor the thin filaments.

    • A band: The dark, central region containing the entire length of the thick filaments, including the zone of overlap with thin filaments.

    • I band: The lighter region containing only thin filaments; it spans across two adjacent sarcomeres.

    • H zone: The center of the A band where only thick filaments are present (no thin filaments).

    • M line: The middle of the H zone; contains proteins that hold thick filaments together.

    • Titin filament: An elastic filament that anchors thick filaments to the Z discs.

  • Myofilament Composition:

    • Thick Filaments: Composed of Myosin molecules. Each myosin molecule has a tail and a myosin head (cross-bridge).

    • Thin Filaments: Composed primarily of Actin. It includes components like:

      • Tropomyosin: A protein that covers the myosin-binding sites on actin when the muscle is relaxed.

      • Troponin: A protein complex that binds to calcium (Ca2+Ca^{2+}). When calcium binds, troponin undergoes a conformational change that moves tropomyosin away from the binding sites.

The Neuromuscular Junction (NMJ)

  • Definition: The point of communication between a somatic motor neuron and a skeletal muscle fiber.

  • Components:

    • Axon Terminal / Presynaptic Terminal: The end of the motor neuron containing synaptic vesicles filled with Acetylcholine (ACh).

    • Synaptic Cleft: The tiny space between the axon terminal and the muscle fiber.

    • Motor End Plate / Postsynaptic Membrane: The specialized region of the sarcolemma containing ACh receptors and junctional folds.

  • NMJ Physiology (Steps of Signal Transmission):

    1. A nerve impulse (action potential) arrives at the axon terminal.

    2. Voltage-gated Ca2+Ca^{2+} channels open, and calcium enters the terminal.

    3. Ca2+Ca^{2+} triggers the fusion of synaptic vesicles with the membrane, releasing Acetylcholine into the synaptic cleft.

    4. ACh diffuses across the cleft and binds to ACh receptors (nicotinic) on the motor end plate.

    5. The receptors (cation channels) open, allowing Sodium (Na+Na^+) to enter the muscle cell, leading to depolarization.

    6. If the depolarization is sufficient, it generates a muscle action potential.

    7. Acetylcholinesterase (AChE): An enzyme located in the basement membrane/synaptic cleft that breaks down ACh to stop the signal and allow for relaxation.

Skeletal Muscle Contraction: Sliding Filament Theory

  • Excitation-Contraction Coupling:

    • The generated action potential travels along the sarcolemma and down the T-tubules.

    • This electrical signal triggers the release of Calcium ions (Ca2+Ca^{2+}) from the terminal cisternae of the sarcoplasmic reticulum into the sarcoplasm.

    • Ca2+Ca^{2+} binds to Troponin (specifically the TnC subunit).

    • This causes a conformational change in the troponin-tropomyosin complex, pulling tropomyosin off the myosin-binding sites on actin.

  • The Contraction Cycle:

    1. ATP Hydrolysis: Myosin heads hydrolyze ATP into ADP and Phosphate (PiP_i), becoming reoriented and energized.

    2. Cross-bridge Formation: The energized myosin heads bind to the exposed binding sites on actin.

    3. Power Stroke: The release of ADP and Phosphate causes the myosin head to rotate toward the center of the sarcomere, pulling the thin filament toward the M line.

    4. Detachment: As a new molecule of ATP binds to the myosin head, the cross-bridge detaches from actin.

  • Result of Contraction: The thin filaments slide past the thick filaments. The H zone and I bands narrow, the Z discs move closer together, and the sarcomere shortens. The total length of the thick and thin filaments does not change.

Muscle Relaxation and Pharmacology

  • Relaxation Process:

    • ACh signals must stop; AChE clears remaining ACh.

    • A Ca2+Ca^{2+} active transport pump (Ca2+Ca^{2+}-ATPase) actively pumps calcium back into the sarcoplasmic reticulum.

    • Inside the SR, calcium binds to a protein called Calsequestrin for storage.

    • As sarcoplasmic Ca2+Ca^{2+} levels drop, the troponin-tropomyosin complex moves back to cover the binding sites, and the muscle fiber relaxes.

  • Clinical and Pharmacological Interactions:

    • Botulinum Toxin: Derived from Clostridium botulinum; it prevents the release of ACh from the terminal, causing flaccid paralysis.

    • Lambert-Eaton Myasthenic Syndrome: Auto-antibodies against voltage-gated Ca2+Ca^{2+} channels prevent ACh release.

    • Myasthenia Gravis: Antibodies against postsynaptic ACh receptors, leading to fatigable muscle weakness, ptosis, and diplopia.

    • Curare / Benzylisoquinolinium: Blocks ACh receptors, preventing ACh action (non-depolarizing blockade).

    • Succinylcholine: An AChR agonist that causes NMJ depolarization and results in a depolarizing blockade.

    • Anticholinesterase Inhibitors: Inhibit AChE to increase ACh levels in the NMJ; used therapeutically in Myasthenia Gravis.

Muscle Metabolism and ATP Generation

  • Cellular Respiration Equation:     C6H12O6+6O2→6CO2+6H2O+ATPC_6H_{12}O_6 + 6O_2 \rightarrow 6CO_2 + 6H_2O + \text{ATP}

  • Sources of ATP:

    • Creatine Phosphate: Provides immediate energy for about 15 seconds. ATP transfers energy to creatine for storage as creatine phosphate when the muscle is relaxed. During contraction, the reaction reverses:         ADP+Creatine Phosphate→ATP+Creatine\text{ADP} + \text{Creatine Phosphate} \rightarrow \text{ATP} + \text{Creatine}

    • Anaerobic Respiration (Glycolysis): Breaks down glucose into pyruvic acid, yielding a net gain of 2 ATP2 \, \text{ATP}. If oxygen is low, pyruvic acid is converted to Lactic acid, which enters the blood.

    • Aerobic Respiration: Occurs in the mitochondria. Uses pyruvic acid (from glycolysis), fatty acids, and amino acids in the presence of oxygen (O2O_2) from hemoglobin or myoglobin. This process yields large amounts of ATP, along with heat, water, and CO2CO_2.

Contraction Dynamics and Development

  • Length-Tension Relationship: There is an optimal resting sarcomere length where tension is maximal (approx. 2.2 μm2.2 \, \mu m). Understretching or overstretching reduces the number of possible cross-bridges, lowering tension.

  • The Muscle Twitch (Myogram):

    • Latent Period: Delay between stimulus and onset of contraction (approx. 0−5 msec0-5 \, \text{msec}).

    • Contraction Period: Tension increases as cross-bridges form (approx. 10−40 msec10-40 \, \text{msec}).

    • Relaxation Period: Tension decreases as Ca2+Ca^{2+} is sequestered (approx. 40−100 msec40-100 \, \text{msec}).

  • Frequency of Stimulation:

    • Wave Summation: Increased tension when stimuli arrive before the previous relaxation ends.

    • Unfused Tetanus: Sustained but wavering contraction.

    • Fused Tetanus: Smooth, sustained contraction at high stimulation frequency.

  • Skeletal Muscle Fiber Types:

    1. Slow Oxidative Fibers: High endurance, aerobic.

    2. Fast Oxidative-Glycolytic Fibers: Intermediate properties.

    3. Fast Glycolytic Fibers: High power, quick fatigue, anaerobic.

  • Embryology: Muscles develop from Somites in the embryo (approx. 22 days). Somites differentiate into the Sclerotome (future vertebrae), Myotome (future muscles), and Dermatome (future skin).