When a neuron is stimulated, the membrane potential of the plasma membrane shifts to a less negative value (that is, toward zero). If this depolarization is sufficiently large, it will cause voltage-gated Na + channels in the membrane to open transiently at the site. As these channels flicker open, they allow a small amount of Na + to enter the cell down its steep electrochemical gradient. The influx of positive charge depolarizes the membrane further (that is, it makes the membrane potential even less negative), thereby opening additional voltage-gated Na + channels and causing still further depolarization.

This process continues in an explosive, self-amplifying fashion until, within about a millisecond, the membrane potential in the local region of the neuron’s plasma membrane has shifted from its resting value of about –60 mV to about +40 mV. The voltage of +40 mV is close to the membrane potential at which the electrochemical driving force for movement of Na + across the membrane is zero—that is, the effects of the membrane potential and the concentration gradient for Na + are equal and opposite; therefore Na + has no further tendency to enter or leave the cell.

During an action potential, voltage-gated Na + channels do not act alone. The depolarized axonal membrane is helped to return to its resting potential by the opening of voltage-gated K + channels. These also open in response to depolarization, but not as promptly as the Na + channels, and they stay open as long as the membrane remains depolarized. As the local depolarization reaches its peak, K + ions (carrying positive charge) therefore start to flow out of the cell, down their electrochemical gradient, through these newly opened K + channels—temporarily unhindered by the negative membrane potential that normally restrains them in the resting cell. The rapid outflow of K + through the voltage-gated K + channels brings the membrane back to its resting state much more quickly than could be achieved by K + outflow through the K+ leak channels alone.

Once it begins, the self-amplifying depolarization of a small patch of plasma membrane quickly spreads outward: the Na + flowing in through open Na + channels begins to depolarize the neighboring region of the membrane, which then goes through the same self-amplifying cycle. In this way, an action potential spreads outward as a traveling wave from the initial site of depolarization, eventually reaching the axon terminals.