Phase 0 of the action potential encompasses the rapid depolarization of the myocyte induced principally by the opening of voltage gated sodium channels. The sodium channels open rapidly in response to membrane depolarization and close within 1 to 2 milliseconds in a time-dependent fashion. The conformation of the channels changes, and they enter an inactivated state in which they cannot be recruited to participate in generating a subsequent action potential for a defined inter val. The interval during which the myocyte cannot be stimulated is the absolute refractory period. After the myocyte returns to a hyperpolarized resting potential, the channels cycle through the inactivated state back to the rested or closed conformation and again are available to open in response to a stimulus of sufficient intensity. The rate of recovery of the Na+ channels from voltage-dependent inactivation is one determinant of the cell's ability to generate a subsequent action potential. The refractory period defines the maximal rate at which the cardiac cells will respond to applied stimuli and propagate impulses to neighboring cells. The density of available sodium channels in the cell membrane also determines the rate at which an impulse is conducted from one cell to another. The maximal upstroke velocity of phase 0 (Vmax) is a major determinant of the speed of impulse conduction within the myocardium and therefore is important in initiation and maintenance of arrhythmia. Genetic mutations in the sodium channel resulting in a sustained inward leak current have been identified and underlie one form of the long QT syndrome (LQTS 3).
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