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 microM, phenytoin reduced the current (n = 65). Inhibition was concentration-dependent with a half-maximal inhibitory concentration of 30.9 +/- 0.8 microM. 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 microM. 5. These results suggest that phenytoin affects K+ currents and that this effect might lead to a reduction in neuronal excitability.