Action Potential Generation and Propagation

Resting Membrane Potential - Ion Powerhouse

• RMP: Electrical potential across cell membrane at rest; typically -70 mV to -90 mV.
• Ionic Basis:
  • Predominant K+ Permeability: K+ efflux via leak channels; major RMP determinant.
  • Na+/K+ ATPase Pump: 3Na+ out / 2K+ in. Maintains gradients. 📌 'Salty Banana' (Na+ outside, K+ inside).
  • Intracellular Anions: Non-diffusible (proteins, phosphates); contribute to negativity (Donnan effect).
• Equations:
  • Nernst: $E_{ion} = \frac{RT}{zF} \ln \frac{[ion]{out}}{[ion]{in}}$ (equilibrium potential for one ion).
  • GHK: $V_m = \frac{RT}{F} \ln \frac{P_K[K^+]{out} + P{Na}[Na^+]{out} + P{Cl}[Cl^-]{in}}{P_K[K^+]{in} + P_{Na}[Na^+]{in} + P{Cl}[Cl^-]_{out}}$ (RMP for multiple ions).

⭐ The Na+/K+ ATPase pump's primary role in RMP is maintaining ionic gradients; its direct electrogenic contribution is small (approx. -4 mV).

Action Potential Generation - Spark of Life

• Rapid, transient reversal of membrane potential (nerve impulse) once RMP reaches threshold.
• Threshold Potential: Critical voltage (e.g., -55 mV) for AP firing.
• Phases & Ionic Basis:
  • Depolarization: Stimulus → threshold → rapid opening of voltage-gated $Na^+$ channels (activation gates) → $Na^+$ influx ↑.
  • Overshoot: Membrane potential peaks (~+30 mV). $Na^+$ channel inactivation gates close.
  • Repolarization: Voltage-gated $K^+$ channels open → $K^+$ efflux ↑. $Na^+$ channels inactivated.
  • After-hyperpolarization (AHP): $K^+$ efflux continues (slow $K^+$ channel closing) → membrane more negative than RMP.
  • RMP restored by $Na^+/K^+$ pump & leak channels.
• 📌 $Na^+$ Channel Gates: Activation (m) gates open fast; Inactivation (h) gates close slow.
• All-or-None Law: AP fires fully if threshold met, or not at all.

⭐ Tetrodotoxin (TTX) & Lidocaine block voltage-gated $Na^+$ channels, preventing APs.

• Clinical Link: Channelopathies (e.g., periodic paralysis, epilepsy) from ion channel defects.

Action Potential Properties - Rules of Engagement

• All-or-None Law: AP fires fully if threshold met; amplitude constant.

  ⭐ The All-or-None Law states that an action potential, once triggered by a threshold stimulus, will fire with its full, constant amplitude and waveform, irrespective of further increases in stimulus strength.

• Refractory Periods: Limit firing rate & ensure unidirectional AP flow.
  • Absolute (ARP): No AP. Na+ channels inactivated.
  • Relative (RRP): Suprathreshold stimulus for AP. Some Na+ channels reset, K+ efflux.

• Accommodation: Slow depolarization ↓ excitability (Na+ inactivation).

Action Potential Propagation - Nerve Express

• Propagation: Local circuit currents (electrotonic spread).
• Conduction Types:
  • Continuous: Unmyelinated; slower, ↑ energy cost.
  • Saltatory: Myelinated; AP "jumps" Nodes of Ranvier (VG Na+ concentrated). Faster, efficient. 📌 Myelin makes it Mighty fast & Jumps like a Hare.

    ⭐ Saltatory conduction not only significantly increases conduction velocity (up to 50 times) but also conserves metabolic energy by restricting ion flow to the Nodes of Ranvier.

• Factors Affecting Velocity:
  • Myelination: Presence & thickness ↑ velocity.
  • Axon Diameter: ↑ Diameter (↓ axial resistance) → ↑ velocity.
  • Temperature: ↑ Temperature → ↑ velocity.
• Safety Factor: Current generated > threshold current needed; ensures reliable propagation.
• Clinical: Demyelination (e.g., MS, GBS) ↓ conduction velocity.

High‑Yield Points - ⚡ Biggest Takeaways

• RMP (approx. -70mV) is set by K+ leak channels & Na+/K+ ATPase.
• Threshold (approx. -55mV) triggers voltage-gated Na+ channel opening for rapid depolarization (Na+ influx).
• Repolarization results from K+ efflux through voltage-gated K+ channels.
• All-or-None Law: AP fires completely if threshold is met, otherwise not at all.
• Absolute Refractory Period: No new AP due to inactivated Na+ channels.
• Saltatory Conduction: Faster AP propagation in myelinated axons via Nodes of Ranvier.