Inhibition of delayed rectifier K + channels by phenytoin in rat neuroblastoma cells

1 The action of the anticonvulsant drug phenytoin on K + currents was investigated in neuroblastoma cells by whole‐cell voltage‐clamp recording. 2 Neuroblastoma cells expressed an outward K + current with a voltage‐and time‐dependence which resembled the delayed‐rectifier K + current found in other cells. When added to the standard external solution at concentrations ranging between 1 and 200 μM, phenytoin reduced the current ( n = 65). Inhibition was concentration‐dependent with a half‐maximal inhibitory concentration of 30.9 + 0.8 μM. 3 The K + current inhibition by phenytoin was voltage‐dependent with block by phenytoin being relieved by depolarization. 4 The times taken to reach steady‐state inhibition and complete recovery from inhibition were about 20 s. Neither the activation and inactivation rates of the K + current nor the K + channel availability were significantly altered by the blocking drug. A use‐dependent block was observed at phenytoin concentrations of 10, 25 and 50 μM. 5 These results suggest that phenytoin affects K + currents and that this effect might lead to a reduction in neuronal excitability.