Depolarization is the first stage of an action potential in a neuron, which is an all-or-nothing event initiated by the opening of sodium ion channels. During depolarization, the membrane potential becomes less negative (more positive) as voltage-gated sodium channels open to allow an influx of sodium ions. This influx of positive sodium ions into the cell leads to further depolarization of the membrane, thus opening more sodium channels in a positive-feedback loop. The depolarization phase lasts approximately 1 millisecond in mature neurons, at which time the sodium channels are inactivated and no longer able to flux ions.

The depolarization of an axon is essential for the transmission of stimuli both within a neuron and between two neurons. Once the stimuli have reached the cell body, the nerve must integrate the various stimuli before the nerve can respond. The stimuli that have traveled down the dendrites converge at the axon hillock, where they are summed to determine the neuronal response. If the sum of the stimuli reaches a certain voltage, known as the threshold potential, depolarization continues from the axon hillock down the axon. The surge of depolarization traveling from the axon hillock to the axon terminal is known as an action potential.

In myelinated axons, depolarizing current from an action potential travels very rapidly through the cytoplasm of axons, insulated by myelin until reaching the next node of Ranvier. At each node, the membrane depolarizes above the threshold voltage, and the influx of sodium ions again initiates the action potential through voltage-gated sodium channels. This pattern of node-to-node propagation, saltatory conduction, can increase the conduction velocity by more than an order of magnitude over unmyelinated axons. In unmyelinated axons, depolarization of the cell membrane must spread to the entire axon, making the propagation significantly slower.