In the generation of the action potential, stimulation of the cell by neurotransmitters (neurotransmitter) or by sensory receptor cells partially opens channel-shaped protein molecules in the membrane. sodium diffuses into the cell, shifting that part of the membrane toward a less-negative polarization. If this local potential reaches a critical state called the threshold potential (measuring about −60 mV), then sodium channels open completely. Sodium floods that part of the cell, which instantly depolarizes to an action potential of about +55 mV. Depolarization activates sodium channels in adjacent parts of the membrane, so that the impulse moves along the fibre.

If the entry of sodium into the fibre were not balanced by the exit of another ion of positive charge, an action potential could not decline from its peak value and return to the resting potential. The declining phase of the action potential is caused by the closing of sodium channels and the opening of potassium channels, which allows a charge approximately equal to that brought into the cell to leave in the form of potassium ions. Subsequently, protein transport molecules pump sodium ions out of the cell and potassium ions in. This restores the original ion concentrations and readies the cell for a new action potential.

The Nobel Prize for Physiology or Medicine was awarded in 1963 to Sir A.L. Hodgkin (Hodgkin, Sir Alan), Sir A.F. Huxley (Huxley, Sir Andrew Fielding), and Sir John Eccles (Eccles, Sir John Carew) for formulating these ionic mechanisms involved in nerve cell activity.