The membrane is depolarized compared to the resting membrane potential.
Through conformational changes from closed, nonconducting states to an open, current-conducting state, membrane depolarization activates sodium channels. Na+ channels open slowly and change from an open state to a nonconducting, rapidly inactivated state as a result of delayed openings, which contribute to the declining fraction of INa induced by prolonged depolarization. Additionally, sodium channels can move swiftly from the closed state to the fast-inactivated state. When the membrane is depolarized, inactivated channels are prevented from opening.
The distribution of channels between the closed and slow-inactivated states, however, limits the number of excitable sodium channels as a function of the membrane potential since slow inactivation acts at greater negative potentials than fast inactivation.
