EFFECTS OF PHENYTOIN ON THE PERSISTENT NA+ CURRENT OF MAMMALIAN CNS NEURONS

WHOLE-Cell recordings in voltage-clamp performed on acutely isolated neurones neocortex and neostriatum to examine the effects of the anticonvulsant phenytoin on a non-inactivating (persistent) Na+ current (I-NaP). I-NaP was chosen because it enhances neuronal excitability near firing threshold, which makes it a potential target for anticonvulsant drugs. In both preparations, phenytoin (10-100 mu M) inhibited I-NaP in a dose-dependent fashion without altering the voltage-dependence of current activation. On average, half-block of I-NaP was produced by 34 mu M phenytoin suggesting that therapeutic drug concentrations are likely to affect I-NaP Inhibition of I-NaP might represent a novel mechanism contributing to the anticonvulsant profile of phenytoin.