Action potential

The action potential is driven by the movement of ions across the plasma membrane through voltage-gated channels. At rest, the membrane potential is maintained near -70 mV by the Na+/K+ ATPase and leak channels, with a high intracellular K+ concentration and high extracellular Na+ concentration. Upon depolarization to a threshold of about -55 mV, voltage-gated Na+ channels open rapidly, allowing Na+ influx that drives the membrane potential toward the Na+ equilibrium potential (~+40 mV). This depolarizing phase is followed by the opening of voltage-gated K+ channels, which repolarize the membrane as K+ exits the cell. The transient inactivation of Na+ channels and the delayed K+ conductance create a refractory period, preventing backward propagation and limiting firing rate.¹

Action potentials propagate along axons without decrement, a property that distinguishes them from passive electrotonic spread. In unmyelinated fibers, propagation is continuous, with each segment of membrane regenerating the signal. In myelinated axons, the myelin sheath acts as an insulator, and action potentials 'jump' between nodes of Ranvier, a process called saltatory conduction. This increases conduction velocity while reducing metabolic cost, as Na+ channels are concentrated at the nodes. The speed of propagation scales with axon diameter; the squid giant axon, which is ~1 mm in diameter, achieves speeds of ~25 m/s, whereas a myelinated vertebrate axon of similar diameter can reach ~100 m/s.²

The modern understanding of the action potential emerged from a series of landmark experiments in the 20th century. In 1939, Alan Hodgkin and Andrew Huxley used the squid giant axon to record intracellular potentials, and in 1952 they published a mathematical model describing the ionic currents, for which they received the Nobel Prize in Physiology or Medicine in 1963. Earlier, Julius Bernstein proposed the membrane theory in 1902, and Kenneth Cole and Howard Curtis measured impedance changes during excitation. The voltage-clamp technique, developed by Cole and George Marmont, was essential for quantifying ion currents. These contributions laid the foundation for computational neuroscience and ion channel pharmacology.³

Beyond neurons and muscle, action potentials occur in other cell types, including pancreatic beta cells, where they trigger insulin release, and in some plant cells, such as the Venus flytrap, which uses electrical signals to snap shut. Cardiac action potentials have a distinctive plateau phase due to L-type Ca2+ channels, lasting ~200 ms. In the nervous system, some neurons fire at rates exceeding 1,000 Hz, such as auditory brainstem neurons, which use specialized Kv3 channels for rapid repolarization. Action potentials can also be induced by electrical stimulation, a principle used in deep brain stimulation for Parkinson's disease. The refractory period is not absolute; a stronger stimulus can sometimes elicit an action potential during the relative refractory period.⁴

Depolarization

A shift in membrane potential toward less negative values, often triggering an action potential.

Voltage-gated ion channel

A membrane protein that opens or closes in response to changes in membrane potential.

Saltatory conduction

Rapid propagation of action potentials in myelinated axons, jumping between nodes of Ranvier.

Refractory period

A brief period after an action potential during which the membrane is less excitable.