Phenytoin Reduces Calcium Current in the Cardiac Purkinje Fiber

SUMMARY. We have investigated the effects of phenytoin on the electrical and mechanical activity of isolated calf and dog cardiac Purkinje fibers. Phenytoin (5-100 HM) 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 rwo-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. (Circ Res 53: 16-23, 1983) PHENYTOIN, also known as diphenylhydantoin (DPH), has been used as a cardiac antiarrhythmic agent since 1958 (Leonard) and as an anticonvulsant since 1938 (Merritt and Putman). However, despite its long history as a clinically effective drug, until recently, little has been known about how it affect