Nerve Muscle Physiology — 15 Marks

(Based on standard Medical Physiology curriculum, per Guyton & Hall / Ganong)

1. Resting Membrane Potential (RMP)

• Actively transports 3 Na⁺ out and 2 K⁺ in per cycle
• Creates a net deficit of positive charges inside → contributes to negativity
• Maintains ionic concentration gradients:
  • Na⁺: 142 mEq/L outside vs. 14 mEq/L inside
  • K⁺: 4 mEq/L outside vs. 140 mEq/L inside

• At rest, the membrane is highly permeable to K⁺ through "leak channels"
• K⁺ diffuses outward down its concentration gradient, leaving behind negatively charged intracellular anions
• This outward diffusion of positive charge is the major contributor to the negative interior

• Large negatively charged proteins trapped inside the cell add to internal negativity

— Guyton and Hall Textbook of Medical Physiology

2. Action Potential in Nerve (Neuron Action Potential)

Stages:

Voltage-Gated Channels:

• Sodium channel has two gates: an activation gate (opens at threshold) and an inactivation gate (closes within <1 ms, ending depolarization)
• Potassium channel opens more slowly — contributes to rapid repolarization

Refractory Periods:

• Absolute refractory period: During peak depolarization to early repolarization — no stimulus can trigger another AP (Na⁺ inactivation gate still closed)
• Relative refractory period: During hyperpolarization — a stronger than normal stimulus can evoke an AP

— Guyton and Hall Textbook of Medical Physiology

3. Neuromuscular Junction (NMJ) / Motor End Plate

Structure:

• A large myelinated motor nerve branches and innervates 3 to several hundred muscle fibres (motor unit)
• The axon terminal lies in a synaptic gutter (trough) — an invagination in the muscle fibre surface
• Synaptic cleft: 20–30 nm wide, contains acetylcholinesterase (AChE)
• Subneural clefts: folds at the bottom of the gutter that amplify the receptor surface area
• Axon terminal contains:
  • ~300,000 acetylcholine (ACh) vesicles
  • Mitochondria (ATP synthesis for ACh production)
  • Voltage-gated Ca²⁺ channels

Transmission of Impulse (Steps):

1. Nerve action potential arrives at the axon terminal
2. Voltage-gated Ca²⁺ channels open → Ca²⁺ flows into the terminal
3. Ca²⁺ activates Ca²⁺-calmodulin-dependent protein kinase → phosphorylates synapsin proteins, releasing ACh vesicles from the cytoskeleton
4. Vesicles dock at active zones adjacent to dense bars → exocytosis releases ~125 vesicles (~125 × 10,000 ACh molecules)
5. ACh diffuses across the synaptic cleft and binds to nicotinic ACh receptors (ligand-gated ion channels) on the postsynaptic muscle membrane
6. ACh-gated channels open → Na⁺ influx + K⁺ efflux → net inward current → end plate potential (EPP)
7. EPP depolarizes the adjacent membrane to threshold → triggers muscle action potential
8. ACh is rapidly destroyed by acetylcholinesterase (AChE) in the synaptic cleft — terminates the signal

— Guyton and Hall Textbook of Medical Physiology

4. Muscle Action Potential & Excitation-Contraction Coupling

Muscle Action Potential:

• RMP of skeletal muscle: –80 to –90 mV
• Duration: 1–5 ms (longer than nerve AP)
• Conduction velocity: 3–5 m/sec (~1/13 that of myelinated nerve)

Spread via T-Tubules:

• The muscle fibre is large — surface AP alone cannot activate deep myofibrils
• Transverse (T) tubules are invaginations of the cell membrane running transversely, communicating with extracellular fluid
• AP spreads along T-tubules to the interior of the fibre

Excitation-Contraction Coupling:

1. T-tubule AP reaches the terminal cisternae of the sarcoplasmic reticulum (SR)
2. Voltage sensor on T-tubule (dihydropyridine receptor, DHPR) mechanically activates ryanodine receptors (RyR) on SR
3. Massive Ca²⁺ release from SR into the sarcoplasm
4. Ca²⁺ binds troponin C → tropomyosin shifts → exposes actin binding sites
5. Myosin heads bind actin → cross-bridge cycling → muscle contraction (sliding filament mechanism)
6. Relaxation: Ca²⁺ pumped back into SR by Ca²⁺-ATPase (SERCA) pump

— Guyton and Hall Textbook of Medical Physiology

5. Clinical Correlates (Pharmacology of NMJ)

Summary Diagram (Conceptual)

Nerve AP → Axon terminal → Ca²⁺ entry → ACh vesicle exocytosis
        → ACh binds nicotinic receptor → EPP
        → Muscle AP → T-tubule → SR Ca²⁺ release
        → Troponin C activation → Cross-bridge cycling → Contraction