INHIBITION OF DELAYED RECTIFIER K-CELLS( CHANNELS BY PHENYTOIN IN RATNEUROBLASTOMA)

1 The action of the anticonvulsant drug phenytoin on K+ currents was i nvestigated in neuroblastoma cells by whole-cell voltage-clamp recordi ng. 2 Neuroblastoma cells expressed an outward Kf current with a volta ge- and time-dependence which resembled the delayed-rectifier K+ curre nt found in other cells. When added to the standard external solution at concentrations ranging between 1 and 200 mu M, phenytoin reduced th e current (n=65). Inhibition was concentration-dependent with a half-m aximal inhibitory concentration of 30.9 +/- 0.8 mu M. 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-s tate inhibition and complete recovery from inhibition were about 20 s. Neither the activation and inactivation rates of the K+ current nor t he K+ channel availability were significantly altered by the blocking drug. A use-dependent block was observed at phenytoin concentrations o f 10, 25 and 50 mu M. 5 These results suggest that phenytoin affects K + currents and that this effect might lead to a reduction in neuronal excitability.