Introduction to Muscle Physiology and Sliding Filament Theory

Muscle Types: Distribution, Control & Examples

• Three macroscopic classes of muscle tissue

  • Skeletal (striated) muscle

  • Directly anchored to bone via tendons → moves the skeleton.

  • Primarily voluntary (somatic motor control)

    • Exception: diaphragm – skeletal in histology but rhythmically driven by autonomic circuits; can be overridden voluntarily (e.g., breath-holding).

  • Cardiac muscle (myocardium)

  • “Myo–” = muscle, “–cardium” = heart → heart muscle.

  • Striated; electrically & mechanically resembles skeletal fibers but specialized for rhythmic, nonstop contraction.

  • Will be revisited in the cardiovascular unit.

  • Smooth muscle

  • Non-striated, spindle-shaped cells.

  • Lines visceral tubes & hollow organs:

    • GI tract (esophagus → large intestine), blood-vessel walls, uterus (myometrium), airways, etc.

  • Controls lumen diameter (e.g., vasoconstriction / vasodilation).

  • Collectively the most abundant muscle type in the body.

Skeletal Muscle Cell (“Muscle Fiber”) Nomenclature

• A muscle fiber = single skeletal muscle cell (avoid confusion with nerve fibers, collagen fibers).

• Specialized terms

  • Sarcolemma: plasma membrane.

  • Sarcoplasm: cytoplasm.

  • Sarcoplasmic reticulum (SR): modified smooth ER

  • Stores high [Ca^{2+}].

  • T-tubule (transverse tubule)

  • Invagination of the sarcolemma that carries extracellular fluid deep into the fiber.

  • Brings the plasma membrane’s electrical events adjacent to the SR.

• Key membrane proteins (arranged triad-style: SR – T-tubule – SR)

  • Nicotinic cholinergic receptor: ligand-gated Na^+ channel opened by ACh.

  • Voltage-gated Na^+ channels: propagate the action potential along sarcolemma/T-tubules (domino analogy).

  • DHP receptor (dihydropyridine receptor)

  • Voltage-sensitive protein (NOT an ion channel in skeletal muscle).

  • Mechanical link to the SR.

  • Ryanodine receptor/channel (RyR) on SR membrane

  • Gate for Ca^{2+} release; physically tethered to DHP.

Excitation–Contraction (E–C) Coupling Sequence (Skeletal)

• 1️⃣ Voluntary command → somatic motor neuron depolarizes, releases acetylcholine (ACh).

• 2️⃣ ACh binds nicotinic receptor → Na^{+} influx → end-plate potential.

• 3️⃣ Depolarization spreads via voltage-gated Na^{+} channels across sarcolemma & down T-tubules.

• 4️⃣ DHP receptor senses voltage → conformational change → pulls on tether → opens RyR.

• 5️⃣ Ca^{2+} efflux from SR into sarcoplasm (down chemical gradient).

• 6️⃣ Raised cytosolic [Ca^{2+}] initiates mechanical contraction (details below).

• Restoration mechanisms

  • \text{Na}^+/\text{K}^+\;\text{ATPase}:\;3\,\text{Na}^+{out}:2\,\text{K}^+{in} (maintains resting gradients & repolarization).

  • Ca^{2+}-ATPase (SERCA) pumps Ca^{2+} back into SR (uses ATP).

  • K^{+} efflux through voltage-gated K^{+} channels repolarizes membrane.

Sarcomere Architecture

• Sarcomere = segment between two Z-discs (zig-zagging anchors).

• Filament system

  • Thick filament: myosin molecules (tails + projecting heads).

  • Thin filament: double helix of F-actin (polymer of G-actin monomers).

  • Regulatory proteins

  • Tropomyosin: rod-shaped, lies in the actin groove, covers myosin-binding sites.

  • Troponin complex: Ca^{2+} sensor attached to tropomyosin.

• Bands & zones

  • H-zone: central region containing only thick filaments (no actin overlap) → shrinks during contraction.

  • As myosin heads pull thin filaments inward, Z-discs move closer, sarcomere shortens, entire fiber shortens generating force.

Calcium’s Regulatory Role

• Resting state: tropomyosin blocks actin’s myosin-binding site → no cross-bridges.

• When SR releases Ca^{2+}

  • Ca^{2+} + Troponin \rightarrow Troponin\text{–}Ca^{2+}

  • Troponin undergoes shape change → drags tropomyosin away → binding sites exposed.

  • Myosin heads can now interact with actin → contraction proceeds.

Sliding Filament Theory (Cross-Bridge Cycle)

(The fiber is already Ca^{2+}-activated.)

1. Detachment / Resting (cocked) state

   • Myosin head contains bound ATP.

   • Head is at ~90^\circ, NOT attached to actin.

2. ATP hydrolysis → Cross-bridge formation

   • Myosin ATPase splits ATP ⇒ ADP + Pi (still attached).

   • Energy flips head to vertical (energized) position & magnetically docks to exposed G-actin site → cross-bridge.

3. Power stroke

   • Release of ADP + Pi → conformational snap (~45^\circ) → head pivots, pulls thin filament toward sarcomere center.

   • H-zone narrows; force/shortening occurs.

4. Rigor state

   • Head remains bound after power stroke (no nucleotide attached).

   • Comparable to rigor mortis in whole-body post-mortem contractions (ATP depleted 12–24 h after death → sustained shortening until proteolysis).

5. ATP binding → Cross-bridge detachment

   • New ATP binds the empty site → affinity for actin decreases → head releases.

   • Cycle can restart once ATP is hydrolyzed again.

Notes & analogies:

• Think of sliding doors: myosin heads are the hands pulling the doors (thin filaments) together.

• Electrical propagation likened to a row of dominoes (voltage-gated Na^{+} channels).

• Cross-bridge resembles a tiny bridge an ant could walk across (metaphor from instructor).

• Microscopic “stepping” mechanism mirrors molecular motors (kinesin/dynein) that ferry vesicles down axons.

Ion Pumps, Energy Demand & Homeostasis

• Na^{+}/K^{+} ATPase ensures excitability by re-establishing electrochemical gradients after each action potential.

• SERCA Ca^{2+} pump rapidly terminates contraction so fibers can relax & prepare for next twitch.

• Both pumps are ATP-dependent → skeletal muscle’s high mitochondrial density supports sustained activity.

Everyday & Systemic Context

• Muscle contraction enables tasks from lifting a barbell to chopping garlic to walking/running.

• Smooth muscle control of vessel radius will resurface in vascular resistance & blood-pressure regulation.

• Cardiac muscle contraction follows many of the same filament principles but with Ca^{2+}-induced-Ca^{2+} release & intercalated-disc synchrony (preview).

• Understanding E–C coupling informs clinical topics: neuromuscular blockers (target nicotinic receptors), malignant hyperthermia (RyR dysfunction), muscle cramps/spasms (involuntary skeletal contractions).