24-25 Muscle Physiology

Functional Morphology of Skeletal Muscle

• Muscle → Fascicles (bundles) → Muscle Fiber (cell) → Myofibrils → Myofilaments (actin/myosin).

• Muscles are composed of fascicles (bundles of muscle fibers).

• Muscle Fiber (Cell): Long, cylindrical cell with multiple nuclei. Contains:

  • Myofibrils: Thread-like structures packed with actin (thin filaments) and myosin (thick filaments)

  • Sarcolemma connects to tendons

  • Sarcoplasmic Reticulum (SR): Calcium storage network surrounding myofibrils.

  • T-Tubules: Invaginations of the sarcolemma that transmit action potentials to the SR.

• Supportive layers of connective tissue surround muscle fibres

  • Endomysium – surrounds individual muscle fibres

  • Perimysium – surrounds a bundle of muscle fibres forming a fascicle (functional unit)

  • Epimysium – surrounds the entire muscle

• Sarcomere: Functional unit of contraction, bounded by Z-discs (anchor actin). Contains:

  • A-band: Dark region with overlapping actin and myosin.

  • I-band: Light region with actin only.

  • H-zone: Central region of A-band with myosin only (shortens during contraction).

• Titin: Giant elastic protein connecting myosin to Z-discs, maintaining sarcomere structure.

Mechanism of Contraction of Skeletal Muscle: Sliding Filament Theory

1. Excitation-Contraction Coupling:

   • Motor neuron releases ACh, triggering muscle membrane depolarization

   • AP generated at the neuromuscular junction travel along the sarcolemma and down into the transverse tubule (T-tubule) system to depolarise the cell membrane

   • Depolarisation of the sarcolemma → opening of voltage-gated L-type Ca²⁺ channels (dihydropyridine receptors), allowing Ca²⁺ to enter the cell

   • Ca²⁺ influx leads to activation of ryanodine receptors located in the SR, which allows Ca²⁺ to flow from the SR into the cytoplasm and further increases intracellular Ca²⁺ concentration

   • Ca²⁺ binds to troponin-c, inducing a conformational change which exposes a binding site on actin for the myosin head

   • Results in ATP hydrolysis, providing energy for the actin and myosin filaments to slide past each other and shorten the sarcomere length, thereby initiating muscle contraction

2. Cross-Bridge Cycling:

   • Attachment: Myosin heads (energized by ATP hydrolysis) bind actin.

   • Power Stroke: Myosin heads pivot, pulling actin toward sarcomere center (ADP + Pi released).

   • Detachment: ATP binds myosin → head releases actin.

   • Reset: ATP split to ADP + Pi by myosin ATPase → head repositions for next cycle.

   • "Walk-Along" Mechanism: Repeated cycles cause filaments to slide, shortening sarcomeres (I-bands narrow; H-zone disappears).

3. Relaxation:

   • Ca²⁺ Reuptake: SR’s Ca²⁺-ATPase pumps Ca²⁺ back into SR.

   • Tropomyosin re-blocks actin sites → muscle returns to resting length (passive process)

Energetics of Contraction of Skeletal Muscle

• ATP Roles:

  • Powers myosin detachment and resetting.

  • Fuels Ca²⁺ pumps in SR.

• Creatine Phosphate: Rapidly regenerates ATP during short bursts.

• Fatigue: Caused by ATP depletion, lactic acid buildup, or ion imbalances (K⁺, Ca²⁺).

• Oxygen Debt: Excess post-exercise O₂ consumption to replenish ATP, clear lactate, and restore ions.

Types of Skeletal Muscle Contractions

• Isotonic: shortens against a constant load (e.g., lifting weights).

• Isometric: Muscle tension without shortening (e.g., holding a plank).

• Eccentric: lengthens under tension (e.g. lowering a lift slowly)

• Summation: rapid stimuli → increased force → graded muscle response

• Tetanus: fused stimuli → sustained contraction/no relaxation → maximal muscle force

• Twitch: Single contraction-relaxation cycle

Muscle Fiber Types

Skeletal Muscle Work & Fatigue

• Work = Force × Distance.

• Power = Work/Time.

• Fatigue Mechanisms:

  • Peripheral: ATP depletion, lactic acid buildup, ionic imbalances (K⁺, Ca²⁺), glycogen loss.

  • Central: CNS inhibition (protective mechanism).

• Recovery: Requires O₂ to restore ATP, clear lactate, and normalize ions.

Electromyography (EMG)

• Principle: Records electrical activity of muscle fibers during contraction.

  • Motor Unit Action Potentials (MUAPs): Summed depolarization of fibers in a motor unit.

• Clinical Uses:

  • Diagnose neuromuscular disorders (e.g., myasthenia gravis, ALS).

  • Assess muscle recruitment patterns in sports science.

  • Hypertrophy: Resistance training → increased myofibrils (not cell number).

  • Atrophy: Disuse → proteolysis (e.g., bed rest, denervation).

  • Denervation: Muscle fibers atrophy; replaced by fibrous tissue (contractures if untreated).

  • Rigor Mortis: Post-mortem ATP depletion → permanent cross-bridge attachment (stiffness).

  • Muscular Dystrophy: Genetic defects in dystrophin → sarcolemma instability.

  • Myasthenia Gravis: Autoimmune attack on ACh receptors → muscle weakness.

Functional Morphology of Smooth Muscles

• No Sarcomeres: Actin/myosin arranged in lattice (attached to dense bodies).

• Caveolae: Membrane invaginations (store Ca²⁺, similar to T-tubules).

• Gap Junctions: Allow electrical coupling in unitary smooth muscle (e.g., gut).

• Unitary (Single-Unit) Smooth Muscle:

  • Structure: Sheets of fibers connected by gap junctions (electrical syncytium)

  • Control: Self-excitatory (pacemaker cells), hormones, stretch, or neurotransmitters

  • Example: Gut, uterus, blood vessels (visceral organs)

• Multi-Unit Smooth Muscle:

  • Structure: Discrete, independent fibers (no gap junctions)

  • Control: Primarily by autonomic nerves (e.g., iris muscles, piloerector muscles)

  • Example: Adjusts pupil size or causes hair erection

Excitation & Electrophysiology of Smooth Muscle

• Depolarization Mechanisms:

  • Autonomic Nerves: Release ACh/norepinephrine → activate receptors.

  • Pacemaker Cells: Generate slow waves (e.g., gut interstitial cells of Cajal).

  • Stretch: Opens mechanosensitive channels → depolarization.

• Action Potentials:

  • Spike Potentials: Brief (10–50 ms) → phasic contractions (e.g., peristalsis).

  • Plateau Potentials: Sustained depolarization → tonic contractions (e.g., blood vessels).

Smooth Muscle - Mechanism of Contraction

• Membrane depolarisation → open L-type voltage-gated calcium channels → extracellular Ca²⁺ enters the cell down its concentration gradient

• Calmodulin-Dependent:

  • Intracellular Ca²⁺ binds calmodulin → activates myosin light-chain kinase (MLCK) → phosphorylates myosin → cross-bridge cycling.

  • Latch State: Myosin phosphatase dephosphorylates myosin → slow detachment → sustained tension.

• Calcium Sources:

  • Extracellular: Via voltage-gated (L-type) or receptor-operated channels

  • Sarcoplasmic Reticulum: IP₃ or Ca²⁺-induced Ca²⁺ release

• Latch Mechanism:

  • Sustained contraction with minimal ATP use.

  • Myosin remains attached to actin even after dephosphorylation (via myosin phosphatase).

• Cross-bridge cycling is slower than in skeletal muscle → energy-efficient, prolonged contractions

Smooth Muscle Disorders

• Hypertension: Overactivation of vascular smooth muscle (e.g., angiotensin II, endothelin).

• Asthma: Bronchial smooth muscle contraction (treated with β₂-agonists like albuterol).

• Erectile Dysfunction: Smooth muscle relaxation in penile arteries mediated by NO (treated with PDE5 inhibitors like sildenafil).

• Tocolytics: Drugs that relax uterine smooth muscle (e.g., magnesium sulfate to delay preterm labor).