At rest, the membrane potential of a typical neuron is about -70 millivolts. This is maintained by the action of the sodium-potassium pump, which constantly moves sodium ions (Na+) out of the cell and potassium ions (K+) into the cell, against their electrochemical gradients.

Activity in cells that synapse onto a neuron can result in their release of various neurotransmitters. These substances can bind to sites on the neuron, directly or indirectly resulting in the opening of ion channels in the cell membrane, allowing for the movement of certain ions (depending on the type of ion channel) according to their electrochemical gradient. If this ionic movement results in a depolarization of the membrane to -50 millivolts, then an action potential will occur.

The depolarization of the membrane to -50 millivolts causes voltage-gated sodium channels to open, momentarily allowing Na+ to flow freely into the neuron, depolarizing the cell further and causing more voltage-gated sodium channels to open. As a result, the membrane potential rapidly reaches peak depolarization, at about +40 millivolts. The depolarization also opens voltage gated potassium channels, and K+ flows out of the cell, which repolarizes the membrane. The depolarization resulting from an action potential is often followed by a brief hyperpolarization of the membrane as a result of the delayed closure of potassium channels.

The action potential is propagated down unmyelinated axons because the initial depolarization perpetuates itself by causing nearby sodium channels to open. In axons with myelin, the depolarization results in a flow of current through the axon that is boosted by the opening of sodium channels at the nodes of ranvier.