Phenytoin reduces calcium current in the cardiac Purkinje fiber

We have investigated the effects of phenytoin on the electrical and mechanical activity of isolated calf and dog cardiac Purkinje fibers. Phenytoin (5-100 microM) lowers and shortens the plateau phase of the Purkinje fiber action potential and reduces twitch tension. We studied the ionic basis of these effects by combining a conventional two-microelectrode voltage clamp procedure with pharmacological techniques that allow separation of time-dependent plateau membrane currents. We find that phenytoin reduces voltage-dependent calcium current in the Purkinje fiber. In addition, this drug slightly reduces two time-dependent outward currents. These effects of phenytoin on membrane current account, at least in part, for its influence on the action potential and twitch tension.