Nerve Muscle Physiology

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Nerve Muscle Physiology — Key Facts for NEET PG

• Resting membrane potential: −70 mV; K⁺ leak channels maintain this
• Action potential phases: Depolarization → overshoot → repolarization → hyperpolarization
• Nerve conduction: Saltatory conduction in myelinated fibers (↑ velocity)
• Neuromuscular junction: Motor end plate — acetylcholine released → end plate potential → muscle AP
• ⚡ Exam tip: Myasthenia gravis = antibodies against ACh receptors; Lambert-Eaton = antibodies against Ca²⁺ channels

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Nerve Muscle Physiology — NEET PG Study Guide

Nerve Cell Physiology

Neuron Structure:

• Cell body (soma): Contains nucleus, Nissl bodies (RER)
• Dendrites: Receive signals
• Axon: Conducts action potentials
• Axon terminal: Releases neurotransmitters at synapse

Resting Membrane Potential:

• Value: −70 mV (inside negative)
• Maintained by: K⁺ leak channels + Na⁺/K⁺-ATPase
• K⁺ equilibrium potential = −90 mV (drives K⁺ out → negative inside)
• ⚡ Exam tip: Na⁺/K⁺-ATPase is electrogenic (3 Na⁺ out, 2 K⁺ in) — contributes to negativity

Action Potential

Phases of Action Potential (in nerve fiber):

Phase	Membrane Potential	Key Events
Resting	−70 mV	Stable
Depolarization	−70 → +30 mV	Na⁺ channels open, Na⁺ influx
Overshoot	+30 mV	Peak (Na⁺ permeability max)
Repolarization	+30 → −70 mV	Na⁺ channels close, K⁺ channels open
Hyperpolarization	−70 → −90 mV	K⁺ efflux continues briefly
Return to resting	−70 mV	Na⁺/K⁺-ATPase restores

Properties:

• All-or-none law: Once threshold is reached, AP amplitude is constant
• Refractory period: Absolute (cannot fire) + Relative (needs stronger stimulus)
• Threshold: ~−55 mV (membrane potential at which enough Na⁺ channels open)
• Conduction velocity: Faster in larger diameter fibers and myelinated fibers

⚡ Exam tip: Myelinated fibers conduct via saltatory conduction — AP jumps between Nodes of Ranvier (120 m/s vs 0.5–2 m/s in unmyelinated)

Synaptic Transmission

Chemical Synapse:

1. Presynaptic terminal receives AP
2. Ca²⁺ enters via voltage-gated channels
3. Vesicles fuse with presynaptic membrane (SNARE proteins)
4. Neurotransmitter released into synaptic cleft
5. Binds postsynaptic receptors
6. Postsynaptic response (EPSP or IPSP)
7. Neurotransmitter cleared (reuptake, degradation, diffusion)

Key Neurotransmitters:

Neurotransmitter	Location	Function
Acetylcholine	NMJ, parasympathetic	Excitatory at NMJ and autonomic ganglia
Norepinephrine	Sympathetic postganglionic	Mostly excitatory
Dopamine	Basal ganglia, midbrain	Movement, reward
Serotonin	Raphe nuclei	Mood, sleep
GABA	CNS	Inhibitory (Cl⁻ channel)
Glutamate	CNS	Excitatory (AMPA, NMDA, kainate receptors)
Glycine	Spinal cord	Inhibitory (Cl⁻ channel)

⚡ Exam tip: GABA is the main inhibitory neurotransmitter in CNS — benzodiazepines enhance GABA action

EPSP vs IPSP:

• EPSP: Depolarizing (Na⁺ or Ca²⁺ influx) — excitatory
• IPSP: Hyperpolarizing (Cl⁻ influx or K⁺ efflux) — inhibitory
• Temporal and spatial summation at axon hillock determines whether AP fires

Neuromuscular Junction

Structure:

• Motor neuron axon terminal → motor end plate (specialized region of muscle membrane)
• Synaptic cleft (~50 nm) with basal lamina containing AChE

Steps:

1. AP arrives at axon terminal → voltage-gated Ca²⁺ channels open
2. Ca²⁺ entry → synaptic vesicles fuse (v-SNARE: synaptobrevin)
3. ACh released via exocytosis
4. ACh binds nicotinic ACh receptors (ligand-gated Na⁺/K⁺ channels)
5. End plate potential (EPP) generated — graded, depolarizing
6. If EPP > threshold → muscle fiber AP fires
7. AChE hydrolyzes ACh → choline reuptake

⚡ Exam tip: One motor neuron innervates many muscle fibers; one muscle fiber has ONE end plate

Muscle Contraction

Sarcomere Structure (organized in series):

• Z-lines: Anchor actin filaments
• I-band: Thin filaments only (isotropic under polarized light)
• A-band: Overlap of thick + thin filaments (anisotropic)
• H-zone: Thick filaments only (center of A-band)
• M-line: Center of sarcomere (connects myosin)
• I-band shortens during contraction; H-zone shortens; A-band unchanged

Contraction Mechanism (Sliding Filament Theory):

1. AP in muscle t-tubule → DHP receptors → Ca²⁺ release from SR
2. Ca²⁺ binds troponin C → tropomyosin moves off actin active sites
3. Myosin head binds actin → power stroke → filament sliding
4. ATP binds myosin head → releases from actin
5. ATP hydrolysis re-cocks myosin head

Muscle Contraction Steps:

Step	Key Events
Excitation	Muscle AP → t-tubules → Ca²⁺ release
Activation	Ca²⁺ binds troponin → tropomyosin shifts
Crossbridge cycling	Myosin-actin interaction → sliding
Relaxation	Ca²⁺ pumped back into SR (SERCA)

⚡ Exam tip: Isotonic contraction = constant tension, changing length; Isometric = constant length, increasing tension

Muscle Fiber Types

Property	Type I (Slow Oxidative)	Type IIa (Fast Oxidative)	Type IIb (Fast Glycolytic)
Color	Red	Pink	White
Myosin ATPase	Slow	Fast	Fast
Contraction speed	Slow	Fast	Fast
Fatigue resistance	High	Moderate	Low
Examples	Postural muscles	Mixed muscles	Extraocular muscles
Mitochondria	Many	Many	Few
Glycogen	Low	Moderate	High

⚡ Exam tip: Denervation → atrophy; disuse → atrophy; increased use → hypertrophy

Excitation-Contraction Coupling

T-tubule System:

• Invaginations of sarcolemma
• Bring AP deep into muscle fiber
• DHP receptors (voltage sensors) on t-tubule membrane
• RyR (ryanodine receptors) on SR

Sequence:

1. AP propagates along sarcolemma → into t-tubules
2. DHP receptors sense voltage change
3. Conformational change in RyR receptors → Ca²⁺ release from SR
4. Ca²⁺ binds troponin → contraction
5. SERCA pump (Ca²⁺-ATPase) pumps Ca²⁺ back into SR
6. Calsequestrin stores Ca²⁺ in SR

Neuromuscular Disorders

Disorder	Pathophysiology	Key Features
Myasthenia gravis	Autoantibodies against ACh receptors	Fatigable weakness, ptosis, diplopia
Lambert-Eaton myasthenic syndrome	Autoantibodies against presynaptic Ca²⁺ channels	Improves with use, proximal weakness
Muscular dystrophy	Dystrophin gene mutation (Duchenne)	Progressive muscle weakness
Myotonia	Chloride channel mutation	Delayed relaxation after contraction

⚡ Exam tip: Edrophonium (Tensilon) test — improves myasthenia gravis but not Lambert-Eaton

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Nerve Muscle Physiology — Comprehensive NEET PG Notes

Detailed Ion Channel Physiology

Voltage-Gated Na⁺ Channels:

• α-subunit: 4 domains, each with 6 transmembrane segments
• Fast channels: Open rapidly, fast inactivation (Nav1.1–Nav1.9)
• States: Closed (resting) → Open (depolarization) → Inactivated (refractory)
• Local anesthetics (lidocaine) block Na⁺ channels — preferentially block pain fibers

Voltage-Gated K⁺ Channels:

• Open during repolarization
• Delayed rectifier channels
• Mutations → long/short QT syndrome

Leak Channels:

• Always open
• Primarily K⁺ leak channels → determine resting potential
• Goldman equation: Incorporates relative permeabilities of Na⁺, K⁺, Cl⁻

** Goldman-Hodgkin-Katz Equation**:

• E(membrane) = RT/F × ln([K⁺]out × Pk + [Na⁺]out × PNa + [Cl⁻]in × PCl) / ([K⁺]in × Pk + [Na⁺]in × PNa + [Cl⁻]out × PCl)
• At 37°C: E ≈ 61.5 × log₁₀(permeability-weighted concentration ratio)

Detailed Synaptic Physiology

Synaptic Integration:

• Temporal summation: Multiple EPSPs from same synapse in quick succession
• Spatial summation: EPSPs from multiple synapses adding together
• Axon hillock: Site where summation determines if AP fires

Synaptic Vesicle Pools:

• Ready-release pool: Docked at active zone
• Refill pool: Recycling vesicles
• Reserve pool: Mobilized slowly

SNARE Proteins:

• v-SNAREs (synaptobrevin/VAMP): On vesicle
• t-SNAREs (SNAP-25, syntaxin): On target membrane
• Botulinum toxin cleaves SNARE proteins → prevents neurotransmitter release

⚡ Exam tip: Botulinum blocks ACh release at NMJ → flaccid paralysis; Tetanus toxin blocks inhibitory neurotransmitters (GABA, glycine) → spastic paralysis

Receptors at Synapse:

Ionotropic receptors (ligand-gated ion channels):

• Fast response (ms)
• Examples: Nicotinic AChR, GABAₐ, NMDA, AMPA

Metabotropic receptors (GPCRs):

• Slow response (s to min)
• Examples: Muscarinic AChR, GABAᵦ, mGluRs

Types of Nerve Fibers (Erbs and Lloyd)

Fiber Type	Diameter	Myelin	Conduction Velocity	Function
Aα	13–20 μm	Yes	80–120 m/s	Motor, proprioception
Aβ	6–12 μm	Yes	40–70 m/s	Touch, pressure
Aγ	3–6 μm	Yes	15–30 m/s	Muscle spindle efferents
Aδ	1–5 μm	Yes	5–15 m/s	Pain, temperature (fast)
B	1–3 μm	No	3–15 m/s	Autonomic preganglionic
C	0.5–1.5 μm	No	0.5–2 m/s	Pain, temperature (slow), autonomic

⚡ Exam tip: First pain (fast, Aδ) vs second pain (slow, C fibers) — different conduction velocities

Detailed Neuromuscular Junction

End Plate Potential:

• Miniature EPPs (MEPPs): Spontaneous vesicle release of ACh
• One vesicle = one quantum of ACh
• EPP = sum of many quanta (synchronized release)
• Quantum content ~200 in normal NMJ

ACh Receptor Subunits:

• Nicotinic AChR: 2α + β + δ + ε (2 binding sites for ACh)
• γ-subunit in fetal form, ε-subunit in adult (adult form has higher conductance)
• Channel conducts Na⁺ and K⁺ (roughly equally)

Drugs Affecting NMJ:

Drug	Mechanism	Effect
Succinylcholine	Depolarizing blocker	Binds AChR, persistent depolarization
Non-depolarizing (curare, rocuronium)	Competitive antagonist	Blocks ACh binding
AChE inhibitors (neostigmine)	Inhibit AChE	↑ ACh at cleft

⚡ Exam tip: Myasthenia gravis patients are sensitive to depolarizing blockers (succinylcholine) and resistant to non-depolarizing blockers

Detailed Muscle Contraction Physiology

Crossbridge Cycling:

1. Cocked state: Myosin head bound to ADP + Pi
2. Power stroke: Release Pi → actin filament slides (5–10 nm per stroke)
3. Rigor state: Myosin-ADP binds actin (brief)
4. New ATP binds: Myosin releases actin
5. ATP hydrolysis: Re-cocks myosin head

Energy Sources for Muscle:

1. ATP (immediate): Used for crossbridge cycling and Ca²⁺ pump
2. Phosphocreatine (short-term): Regenerates ATP via creatine kinase
3. Glycolysis (moderate): Anaerobic → 2 ATP/glucose (lactate accumulates)
4. Oxidative phosphorylation (long-term): Aerobic → 36 ATP/glucose

Oxygen Debt:

• Lactate produced during exercise must be cleared
• Requires O₂ to metabolize lactate (Cori cycle in liver)
• Explains increased ventilation after exercise

Muscle Mechanics

Length-Tension Relationship:

• Optimal length: Maximum overlap of actin/myosin → maximum tension
• Shorter length: Overlap too much → interference
• Longer length: Less overlap → fewer crossbridges possible

Force-Velocity Relationship (Hill’s equation):

• Load (isotonic): More load → slower contraction
• No load: Maximum velocity
• Maximum isometric tension at zero velocity

Types of Contractions:

• Concentric: Muscle shortens (lifting weight)
• Eccentric: Muscle lengthens (lowering weight)
• Isometric: Muscle tension changes but length constant

⚡ Exam tip: Eccentric contractions cause more muscle damage and DOMS (delayed onset muscle soreness)

Smooth Muscle Physiology

Types:

Feature	Single-unit (Visceral)	Multi-unit
Arrangement	Gap junctions	Independent
Pacemaker cells	Yes (slow waves)	No
Control	Involuntary (autonomic)	Voluntary (autonomic)
Examples	GI tract, uterus, blood vessels	Airways, large arteries, ciliary muscle

Key Differences from Skeletal Muscle:

• No sarcomeres (actin and myosin not organized)
• Contraction regulated by Ca²⁺/calmodulin pathway
• Denervation causes less atrophy
• Can exhibit tetanus? No (slow contraction, no summation)

Ca²⁺-Calmodulin Pathway:

1. [Ca²⁺]i ↑ → binds calmodulin
2. Ca²⁺-calmodulin activates MLCK (myosin light chain kinase)
3. MLCK phosphorylates myosin light chain → crossbridge cycling
4. MLCP (phosphatase) dephosphorylates → relaxation

⚡ Exam tip: Smooth muscle tone regulated by MLCK/MLCP balance; GPCRs linked to Gq → PLC → IP₃ → Ca²⁺ → contraction

Regeneration and Repair

Nerve Regeneration:

• PNS: Axon can regrow at ~1 mm/day; Schwann cells guide regeneration
• CNS: No regeneration; oligodendrocytes produce inhibitory proteins (Nogo, MAG)

Muscle Regeneration:

• Satellite cells (muscle stem cells) can regenerate
• Extensive damage → fibrosis (scarring)
• Duchenne muscular dystrophy: Mutations in dystrophin → progressive degeneration

Practice Questions for NEET PG

1. Compare the action potential of a nerve fiber with that of a skeletal muscle fiber.
2. Describe the steps of synaptic transmission at a chemical synapse.
3. Explain the sliding filament theory of muscle contraction.
4. A patient with myasthenia gravis is given edrophonium. What is the mechanism and expected response?
5. Compare isotonic and isometric contractions with examples.
6. Describe the excitation-contraction coupling sequence in skeletal muscle.
7. What is the difference between single-unit and multi-unit smooth muscle?

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