Abstract
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.