Teach me Nerve Action Potential Physiology and all for neet PG

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Nerve Action Potential Physiology - Complete NEET PG Guide

Sources: Guyton & Hall (14e), Costanzo Physiology (7e), Ganong's Review (26e)

1. Resting Membrane Potential (RMP)

Definition

The RMP is the potential difference across the membrane of excitable cells between action potentials, expressed as intracellular relative to extracellular potential.
  • Value: -70 mV (nerve) to -90 mV (skeletal muscle)

Why is the inside negative?

Two key mechanisms:
A. Na⁺-K⁺ ATPase Pump (Electrogenic)
Na⁺-K⁺ pump and K⁺ leak channels diagram
  • Pumps 3 Na⁺ OUT and 2 K⁺ IN per cycle (uses ATP)
  • Net effect: 1 positive charge leaves per cycle → creates a net negative charge inside
  • This is an electrogenic pump (contributes ~-4 mV directly)
  • Creates ionic concentration gradients:
IonOutsideInside
Na⁺142 mEq/L14 mEq/L
K⁺4 mEq/L140 mEq/L
B. K⁺ Leak Channels
  • At rest, membrane is highly permeable to K⁺ (K⁺ leak channels are open)
  • K⁺ diffuses OUT down its concentration gradient, taking positive charge with it
  • This dominates RMP calculation
  • Na⁺ permeability at rest is very low
Nernst Equation (for a single ion):
E = (61/z) × log [ion]out/[ion]in
Goldman Equation (for multiple ions - gives RMP):
Em = weighted by relative permeabilities of K⁺, Na⁺, Cl⁻
Key Rule for NEET PG:
RMP is determined mainly by K⁺ because K⁺ permeability is highest at rest. If K⁺ equilibrium potential = -94 mV and Na⁺ equilibrium potential = +61 mV, the RMP (-70 mV) sits close to K⁺.
  • Costanzo Physiology 7e, p. 26

2. Action Potential - Step by Step

Action potential waveform showing depolarization, overshoot, repolarization, hyperpolarization

Stages (Guyton & Hall)

StageMembrane PotentialWhat Happens
Resting-70 mVPolarized state; membrane at rest
Threshold-55 mVStimulus depolarizes to this point; Na⁺ channels open explosively
Depolarization (Upstroke)-70 → +35 mVRapid Na⁺ influx; membrane becomes positive inside
Overshoot+35 mVPotential overshoots zero; approaches Na⁺ equilibrium (+61 mV)
Repolarization+35 → -70 mVNa⁺ channels inactivate; K⁺ channels open → K⁺ efflux
Hyperpolarization (Undershoot)-70 → -80 mVK⁺ channels remain open longer; membrane transiently more negative
Return to RMPBack to -70 mVK⁺ channels close; Na⁺-K⁺ pump restores gradients
  • Guyton & Hall, p. 80

3. Ionic Basis of the Action Potential

Voltage and conductance changes during action potential - Na⁺ and K⁺ conductance curves with refractory periods

Voltage-Gated Na⁺ Channel (VGNC) - "M-gate / H-gate"

The Na⁺ channel has 2 gates:
  • Activation gate (M-gate): Opens rapidly on depolarization → triggers upstroke
  • Inactivation gate (H-gate): Closes slowly on depolarization → ends upstroke
Channel StateActivation GateInactivation GateIon Flow
Closed (resting)ClosedOpenNone
OpenOpenOpen (briefly)Na⁺ IN
InactivatedOpenClosedNone
Recovery: Only when the cell repolarizes back toward RMP do inactivation gates re-open → channels return to "closed but available" state.

Voltage-Gated K⁺ Channel

  • Opens slowly after depolarization
  • Stays open during repolarization and into hyperpolarization
  • Causes K⁺ efflux → repolarization and undershoot
Key Drugs Blocking Na⁺ Channels (NEET PG High-Yield):
  • Tetrodotoxin (TTX) - from puffer fish - blocks from outside
  • Local anesthetics (lidocaine) - block from inside, use-dependent
  • Both block the voltage-sensitive Na⁺ channels and prevent action potentials
  • Costanzo Physiology 7e, p. 28-30

4. Characteristics of the Action Potential

Three fundamental properties:
  1. All-or-None Law: AP either fires completely or not at all - no partial AP (once threshold is reached, the full response occurs)
  2. Stereotypical size and shape: Every normal AP for a given cell type looks identical
  3. Non-decremental propagation: AP does not decrease in amplitude as it travels along the nerve fiber

5. Refractory Periods

Absolute Refractory Period (ARP)

  • Lasts from threshold until ~1/3 of repolarization
  • No AP possible no matter how strong the stimulus
  • Basis: Na⁺ inactivation gates are CLOSED (Na⁺ channels in inactivated state)
  • Cannot fire again until membrane repolarizes and inactivation gates reset

Relative Refractory Period (RRP)

  • Begins at end of ARP, overlaps with hyperpolarization
  • AP CAN be elicited but only with a supramaximal stimulus
  • Basis: K⁺ conductance is still higher than at rest → membrane hyperpolarized → needs more inward current to reach threshold
PropertyAbsolute RefractoryRelative Refractory
AP possible?NOYES (with larger stimulus)
BasisNa⁺ inactivation gates closedElevated K⁺ conductance
Timing~1 ms (during AP)~5-10 ms (during hyperpolarization)
Clinical Significance: ARP prevents backward conduction (ensures unidirectional propagation) and limits maximum firing frequency.
  • Ganong's Review, p. (Refractory Periods section)

6. Accommodation

  • When a nerve is depolarized slowly, it may fail to fire an AP even though threshold voltage is crossed
  • Reason: Slow depolarization gives time for Na⁺ inactivation gates to close progressively → insufficient Na⁺ channels available to generate upstroke
  • Clinical example: Hyperkalemia → chronic depolarization → Na⁺ channels inactivated → muscle weakness despite depolarized membrane

7. Propagation of the Action Potential

Unmyelinated Fibers

  • AP propagates by local current circuits - each depolarized area depolarizes the adjacent area
  • Continuous, slow conduction

Myelinated Fibers - Saltatory Conduction

Myelinated and unmyelinated nerve fiber structure with Schwann cells and Node of Ranvier
  • Myelin is formed by Schwann cells (PNS) wrapping around axon
  • Node of Ranvier = uninsulated gap every 1-3 mm
  • AP jumps from node to node (saltatory = "to jump" in Latin)
  • Only nodes have high Na⁺ channel density; internodal membrane has very few
  • Myelin reduces ion flow through internodal membrane ~5000-fold
Advantages of Saltatory Conduction:
  1. Conduction velocity increased 5-50x compared to unmyelinated fibers
  2. Energy-efficient - ion exchange only at nodes, so less Na⁺-K⁺ pump activity needed
Conduction velocity (CV) determinants:
  • Larger diameter → faster CV
  • Myelination → much faster CV
  • Unmyelinated: CV ∝ √(diameter)
  • Myelinated: CV ∝ diameter (linear relationship)
  • Fastest: Aα = 70-120 m/s; Slowest: C fibers = 0.5-2 m/s
  • Guyton & Hall, p. (Saltatory conduction section)

8. Classification of Nerve Fibers (NEET PG Must-Know)

Erlanger-Gasser Classification (Motor + Sensory)

FiberDiameterCV (m/s)MyelinFunction
Largest70-120Yesα-motoneurons, proprioception (Ia, Ib)
Medium30-70YesTouch, pressure
Medium15-30Yesγ-motoneurons to muscle spindles
Small5-30YesFast pain, temperature, touch
BSmall3-15ThinPreganglionic autonomic
CSmallest0.5-2NoSlow pain, temp, postganglionic autonomic

Lloyd-Hunt Classification (Sensory Only)

ClassEquivalentSourceFunction
IaMuscle spindle primary afferentStretch (dynamic)
IbGolgi tendon organTension sensing
IIMuscle spindle secondary, skinTouch, pressure
IIISkinFast pain, temperature
IVCSkinSlow pain, temperature
NEET PG Mnemonics:
  • "ABCD of pain": A-delta = fast/first pain (sharp), C fibers = slow/second pain (burning/aching)
  • C fibers are unmyelinated - only fiber class with no myelin
  • B fibers = preganglionic autonomic (lightly myelinated)
  • Costanzo Physiology 7e, Table 3.1

9. High-Yield NEET PG Points Summary

TopicKey Fact
RMP value (nerve)-70 mV
Threshold potential-55 mV
Na⁺ equilibrium potential+61 mV
K⁺ equilibrium potential-94 mV
Na⁺-K⁺ pump ratio3 Na⁺ out : 2 K⁺ in
Dominant ion at restK⁺ (high permeability)
Upstroke ionNa⁺ (rapid influx)
Repolarization ionK⁺ (efflux)
Hyperpolarization causeK⁺ channels remain open
ARP basisNa⁺ inactivation gates closed
RRP basisElevated K⁺ conductance
Saltatory conduction jumpsNode to Node (of Ranvier)
Fastest fiberAα (70-120 m/s)
Slowest fiberC (0.5-2 m/s); unmyelinated
TTX blocksVoltage-gated Na⁺ channels
AccommodationSlow depolarization → Na⁺ inactivation → no AP
All-or-none lawAP is complete or absent

10. Clinically Relevant NEET PG Scenarios

ConditionPhysiology
Hyperkalemia → muscle weaknessChronic depolarization → Na⁺ channel inactivation → accommodation → no AP
Hypokalemia → weaknessHyperpolarizes membrane → harder to reach threshold
Local anestheticsBlock voltage-gated Na⁺ channels → no AP in sensory/pain fibers
Multiple sclerosisDemyelination → loss of saltatory conduction → slowed/blocked CV
Tetrodotoxin poisoningBlocks Na⁺ channels from outside → paralysis
Hypocalcemia → tetanyCa²⁺ normally stabilizes Na⁺ channels; low Ca²⁺ → increased excitability → spontaneous AP

Quick Recap for Exam Day:
  1. RMP = -70 mV, maintained by K⁺ leak + Na⁺-K⁺ pump
  2. AP: Resting → Threshold (-55) → Depolarization (Na⁺ in) → Overshoot (+35) → Repolarization (K⁺ out) → Hyperpolarization → Back to -70
  3. ARP = Na⁺ channels inactivated; RRP = K⁺ channels still open (hyperpolarized)
  4. Saltatory conduction = node-to-node jumping; 5-50x faster; energy efficient
  5. Fastest = Aα, Slowest = C (unmyelinated); Fast pain = Aδ, Slow pain = C
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