WHOLE-Cell recordings in voltage-clamp performed on acutely isolated n
eurones neocortex and neostriatum to examine the effects of the antico
nvulsant phenytoin on a non-inactivating (persistent) Na+ current (I-N
aP). I-NaP was chosen because it enhances neuronal excitability near f
iring threshold, which makes it a potential target for anticonvulsant
drugs. In both preparations, phenytoin (10-100 mu M) inhibited I-NaP i
n 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 li
kely to affect I-NaP Inhibition of I-NaP might represent a novel mecha
nism contributing to the anticonvulsant profile of phenytoin.