1. Resting Membrane Potential (RMP)

Before an action potential can occur, cells maintain a resting membrane potential, typically around –70 mV in neurons. This is established by:

• Na⁺/K⁺ ATPase pump: Actively transports 3 Na⁺ out and 2 K⁺ into the cell.

• Selective permeability: The membrane is more permeable to K⁺ than Na⁺, allowing K⁺ to leak out, making the inside more negative.

• Anionic proteins: Negatively charged proteins inside the cell contribute to the negative RMP.

2. Phases of the Action Potential

The action potential unfolds in a series of well-defined phases:

a. Depolarization

• Triggered when a stimulus brings the membrane potential to the threshold (around –55 mV).

• Voltage-gated Na⁺ channels open, allowing Na⁺ to rush into the cell.

• The membrane potential rapidly becomes positive, peaking around +30 mV.

b. Repolarization

• Na⁺ channels inactivate, and voltage-gated K⁺ channels open.

• K⁺ exits the cell, restoring the negative membrane potential.

c. Hyperpolarization

• K⁺ channels remain open slightly longer, causing the membrane potential to dip below the resting level (more negative than –70 mV).

• Eventually, the RMP is restored as K⁺ channels close and the Na⁺/K⁺ pump re-establishes ion gradients.

3. All-or-None Principle

Once the threshold is reached, the action potential is irreversible and uniform in magnitude. Subthreshold stimuli do not trigger an action potential, while suprathreshold stimuli do not increase its size—only its frequency.

4. Refractory Periods

These ensure unidirectional propagation and limit firing frequency:

• Absolute refractory period: No new action potential can be initiated, regardless of stimulus strength.

• Relative refractory period: A stronger-than-normal stimulus can trigger another action potential.

5. Propagation of the Action Potential

In neurons, the action potential travels along the axon:

• Continuous conduction: In unmyelinated fibers, the AP moves in a wave-like fashion.

• Saltatory conduction: In myelinated fibers, the AP jumps between nodes of Ranvier, increasing speed and efficiency.

6. Clinical Relevance

Understanding action potentials is vital in:

• Cardiology: Cardiac myocytes have unique AP profiles with plateau phases due to Ca⊃2;⁺ influx.

• Neurology: Disorders like multiple sclerosis involve demyelination, impairing AP propagation.

• Pharmacology: Local anesthetics block Na⁺ channels, preventing AP initiation and pain transmission.

7. Key Ion Channels and Transporters