Action potential Study Guide

📖 Core Concepts Action Potential (AP) – A rapid, all‑or‑none voltage spike caused by coordinated opening of voltage‑gated Na⁺ (or Ca²⁺) channels followed by K⁺ channels. Resting Membrane Potential (RMP) –  –70 mV in most neurons; set by Na⁺/K⁺‑ATPase and leak channels. Threshold –  –55 mV; the membrane voltage at which enough Na⁺ channels open to trigger positive feedback. Saltatory Conduction – In myelinated axons, the AP “jumps” from node of Ranvier to node, greatly increasing speed. Refractory Periods – Absolute (Na⁺ channels inactivated, no AP possible) → Relative (some Na⁺ channels recovered, larger stimulus needed). All‑Or‑Nothing – Once threshold is crossed, the AP waveform is fixed; stimulus strength is encoded by firing frequency, not amplitude. Spike Train – Temporal pattern of successive APs; the basic language of neuronal communication. --- 📌 Must Remember RMP ≈ –70 mV, Threshold ≈ –55 mV. Peak AP ≈ +30 mV (Na⁺‑based spikes). AP duration: fast Na⁺ spikes < 1 ms; Ca²⁺ spikes ≈ 10–100 ms. Absolute refractory ≈ 1 ms (Na⁺ inactivation); Relative refractory lasts a few ms longer (K⁺ channels still open). Myelinated conduction velocity can exceed 100 m/s, 10× faster than unmyelinated fibers of the same diameter. Hodgkin–Huxley: AP = coupled ODEs for Na⁺ activation (m), Na⁺ inactivation (h), and K⁺ activation (n). Na⁺ equilibrium potential $E{\text{Na}} \approx +55\ \text{mV}$; K⁺ equilibrium potential $E{\text{K}} \approx –90\ \text{mV}$. --- 🔄 Key Processes Initiation (Rising Phase) Depolarization → voltage‑gated Na⁺ channels open (m‑gate). Na⁺ influx drives $Vm$ toward $E{\text{Na}}$ → positive feedback. Peak & Inactivation Na⁺ channels reach maximal open probability; simultaneously begin inactivating (h‑gate closes). Voltage‑gated K⁺ channels start opening (n‑gate). Repolarization (Falling Phase) Inactivated Na⁺ channels close → Na⁺ influx stops. K⁺ efflux dominates, pulling $Vm$ back toward $E{\text{K}}$. Afterhyperpolarization (AHP) Some K⁺ channels (e.g., delayed rectifier, Ca²⁺‑activated) remain open longer → $Vm$ undershoots RMP. Propagation (Unmyelinated) Local depolarizing current spreads, brings adjacent segment to threshold → new AP. Propagation (Myelinated – Saltatory) Internodes: high resistance, low capacitance → current flows rapidly to next node. Nodes: dense Na⁺ channels regenerate the AP. Synaptic Release AP reaches terminal → voltage‑gated Ca²⁺ channels open → Ca²⁺ influx → vesicle fusion → neurotransmitter release. --- 🔍 Key Comparisons Na⁺‑based vs. Ca²⁺‑based AP Speed: Na⁺ spikes < 1 ms; Ca²⁺ spikes 10–100 ms. Channels: Voltage‑gated Na⁺ vs. voltage‑gated Ca²⁺. Physiology: Fast signaling in adult neurons; Ca²⁺ spikes common in early development or specialized cells (e.g., cardiac pacemakers). Myelinated vs. Unmyelinated Axons Conduction: Jumping (nodes) vs. continuous wave. Velocity: 10× faster with myelin. Energy use: Fewer ions cross membrane → lower ATP demand. Absolute vs. Relative Refractory Absolute: Na⁺ channels fully inactivated → no AP possible. Relative: Some Na⁺ channels recovered; larger depolarization needed. Graded Potential vs. Action Potential Amplitude: Variable (graded) vs. fixed (AP). Propagation: Decays with distance vs. regenerates at each segment. Encoding: Stimulus strength (graded) vs. firing frequency (AP). --- ⚠️ Common Misunderstandings “Stronger stimulus makes a bigger AP.” – Wrong; stimulus size changes firing rate, not AP amplitude. “All neurons fire the same way.” – Na⁺ spikes dominate adult CNS, but many cells use Ca²⁺ spikes or mixed bursts. “Myelin only speeds conduction; it doesn’t affect safety.” – Myelin also reduces current leak, preserving the amplitude of depolarization between nodes. “Refractory period only matters for timing.” – It also guarantees unidirectional propagation because the rear segment is in the absolute refractory state. --- 🧠 Mental Models / Intuition Positive‑feedback ladder: Think of Na⁺ channels as a row of dominoes; once the first few fall (threshold reached), the rest tumble rapidly, creating the upstroke. Leak‑proof pipe: Myelin is like insulating a water pipe; pressure (current) builds up and is delivered farther without loss, so the “water” (depolarizing current) reaches the next node intact. Gate‑keeper analogy: Na⁺ channels have an activation gate (opens with depolarization) and an inactivation gate (closes shortly after). The AP is the brief window when the activation gate is open but the inactivation gate is still closed. --- 🚩 Exceptions & Edge Cases Anode‑break excitation – A sudden release from a hyperpolarizing current can trigger an AP (not predicted by simple threshold models). Excitation block – Very large depolarizing currents can prevent APs by keeping Na⁺ channels in a non‑conducting state. Back‑propagating spikes – In some pyramidal neurons, APs travel into dendrites, influencing synaptic plasticity. Pacemaker cells – Generate rhythmic APs without external depolarizing input due to spontaneous depolarization currents (e.g., funny current $If$). --- 📍 When to Use Which Predict AP shape? → Use Hodgkin–Huxley for detailed Na⁺/K⁺ dynamics; use FitzHugh‑Nagumo or Morris‑Lecar for qualitative insight. Estimate conduction speed? → Apply cable theory: speed ∝ √(axon diameter) × (myelination factor). Identify drug target? → Tetrodotoxin → Na⁺ channels; Dendrotoxin → K⁺ channels; Verapamil → L‑type Ca²⁺ channels (cardiac plateau). Classify a spike in a developing neuron? → If duration > 30 ms → likely Ca²⁺‑based; if < 2 ms → Na⁺‑based. --- 👀 Patterns to Recognize Rapid upstroke + brief peak → Na⁺‑based spike. Broad plateau (hundreds of ms) → cardiac AP (Ca²⁺ plateau). Burst of spikes followed by silence → interplay of Na⁺ and Ca²⁺ currents. Voltage‑clamp current trace with an early inward Na⁺ transient followed by a delayed outward K⁺ current → classic HH profile. Reduced amplitude in successive spikes during high‑frequency firing → accumulation of Na⁺ channel inactivation (relative refractory). --- 🗂️ Exam Traps “Peak voltage is +55 mV.” – Peak is near +30 mV in neurons; +55 mV is the Na⁺ equilibrium potential, not the actual AP peak. “Myelinated axons have lower resistance.” – Myelin increases membrane resistance in internodes, while decreasing capacitance. “All refractory periods are the same length.” – Absolute refractory is short (1 ms); relative refractory can vary widely with K⁺ channel subtype expression. “Calcium spikes are only found in cardiac muscle.” – Ca²⁺‑based spikes also occur in developing neurons, some endocrine cells, and certain invertebrate neurons. “Voltage‑gated Na⁺ channels are the only channels involved in AP propagation.” – K⁺ channels are essential for repolarization and shaping the refractory periods; without them the AP would not terminate properly. ---