Action Potential Stages

Why This Matters

The action potential is the fundamental language of the nervous system—it's how neurons communicate across distances, from your brain commanding your fingers to type to your sensory neurons signaling pain. You're being tested on more than just memorizing voltage values; exams expect you to understand ion channel dynamics, electrochemical gradients, and the feedback mechanisms that make neural signaling both rapid and reliable. This topic connects directly to synaptic transmission, neural coding, and even pharmacology (since many drugs target specific phases of the action potential).

When you study these stages, focus on the why behind each phase: which ions are moving, which channels are responsible, and how each stage sets up the next. Don't just memorize that resting potential is $-70 \text{ mV}$—know that it exists because of the sodium-potassium pump and leak channels working together. Understanding the mechanism means you can reason through novel questions, predict drug effects, and nail those free-response explanations.

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Setting the Stage: Establishing Membrane Potential

Before a neuron can fire, it must maintain a stable electrochemical gradient. This "ready state" is actively maintained by ion pumps and selective membrane permeability, creating the potential energy that powers the action potential.

Resting State

• Membrane potential sits at approximately $-70 \text{ mV}$—this negative charge reflects the unequal distribution of ions across the membrane
• Sodium-potassium pump ($\text{Na}^+/\text{K}^+$-ATPase) actively transports $3 \text{ Na}^+$ out for every $2 \text{ K}^+$ in, maintaining the concentration gradient at the cost of ATP
• Voltage-gated $\text{Na}^+$ channels are closed while $\text{K}^+$ leak channels remain partially open, making the membrane more permeable to potassium and contributing to the negative resting potential

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Initiation: Reaching Threshold

The transition from rest to action potential depends on reaching a critical voltage. This threshold mechanism ensures that neurons respond in an all-or-none fashion—weak stimuli don't produce weak action potentials; they produce none at all.

Depolarization

• Threshold potential of approximately $-55 \text{ mV}$ must be reached for an action potential to fire—this is the "point of no return"
• Voltage-gated $\text{Na}^+$ channels open in response to initial depolarization, allowing $\text{Na}^+$ to rush down its electrochemical gradient into the cell
• Positive feedback loop drives further depolarization—entering $\text{Na}^+$ opens more $\text{Na}^+$ channels, which admits more $\text{Na}^+$, explaining why the rising phase is so rapid

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The Spike: Rapid Voltage Change

The rising phase and peak represent the most dramatic voltage changes in the action potential. The speed of this phase—often less than 1 millisecond—depends on the density and kinetics of voltage-gated sodium channels.

Rising Phase

• Membrane potential shoots toward $+30 \text{ mV}$ as $\text{Na}^+$ influx overwhelms the resting negative charge
• Regenerative process occurs as depolarization spreads to adjacent membrane regions, opening more voltage-gated $\text{Na}^+$ channels and enabling propagation along the axon
• Neuronal excitability is demonstrated during this phase—neurons with more $\text{Na}^+$ channels or faster channel kinetics show steeper rising phases

Peak

• Maximum depolarization reaches approximately $+30 \text{ mV}$—the membrane briefly becomes positive inside relative to outside
• $\text{Na}^+$ channel inactivation begins as the channels enter a refractory conformation, automatically limiting how positive the membrane can become
• Voltage-gated $\text{K}^+$ channels start opening with a slight delay, setting up the transition to repolarization—this delay is critical for the action potential's shape

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Recovery: Restoring the Gradient

After the spike, the neuron must return to its resting state. This recovery involves both passive ion flow through open channels and the continued work of the sodium-potassium pump to restore original ion distributions.

Repolarization

• $\text{K}^+$ efflux drives the membrane potential negative as voltage-gated $\text{K}^+$ channels reach peak conductance
• $\text{Na}^+$ channels remain inactivated during this phase, preventing any competing sodium influx and ensuring the membrane repolarizes
• Membrane potential returns toward $-70 \text{ mV}$—this phase "resets" the electrical state, though ion concentrations haven't yet been fully restored

Hyperpolarization (Undershoot)

• Membrane potential temporarily dips to approximately $-80 \text{ mV}$—more negative than resting potential
• Delayed $\text{K}^+$ channel closing causes this overshoot; the channels opened in response to depolarization but close slowly after repolarization
• Increased threshold for subsequent firing during this phase contributes to the relative refractory period and ensures unidirectional propagation of action potentials

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Protection: Ensuring Signal Fidelity

The refractory period isn't just recovery time—it's a functional mechanism that shapes how neurons encode information. By limiting firing frequency and ensuring unidirectional propagation, the refractory period transforms action potentials into a reliable signaling system.

Refractory Period

• Absolute refractory period occurs while $\text{Na}^+$ channels are inactivated—no stimulus, regardless of strength, can trigger another action potential
• Relative refractory period follows as channels recover but hyperpolarization persists—a stronger-than-normal stimulus can trigger firing
• Unidirectional propagation is guaranteed because the membrane region that just fired cannot immediately fire again, forcing the action potential to travel forward along the axon

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Quick Reference Table

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Self-Check Questions

1. Which two phases both involve $\text{K}^+$ efflux, and what distinguishes their effects on membrane potential?

2. A neuron is at $-60 \text{ mV}$. Explain whether an action potential will fire and what must happen if it doesn't.

3. Compare and contrast $\text{Na}^+$ channel inactivation at the peak with $\text{Na}^+$ channel closure at rest—why does this distinction matter for the refractory period?

4. If a drug blocked voltage-gated $\text{K}^+$ channels, which phases would be affected and how would the action potential shape change?

5. Using your knowledge of the refractory period, explain why action potentials propagate in only one direction along an axon and how this relates to neural signaling fidelity.