A discriminant block among K+ channel types by phenytoin in neuroblastoma cells

The action of the anticonvulsant drug phenytoin on K+ channels was investigated in neuroblastoma cells (N2A) by using the single-channel patch-clamp technique. N2A cells expressed three types of delayed rectifier K+ channels, which were found to have a conductance of 10-20 pS in a 'physiological' K+ gradient. When added to the external solution at concentrations ranging between 1 and 200 microM, phenytoin decreased single channel activity, whereas the unitary current amplitude was unaffected in all three types of channels. The open probability of the biggest channel decreased, according to an exponential distribution of open and closed times, from 40% in control conditions to 10% in the presence of 50 microM phenytoin (Vm=40 mv). The reduction in the open-channel probability was concentration-dependent with a IC50 = 27.2+/-0.9 microM. A transient type of K channel was identified that was affected by cumulative inactivation and had a conductance of a mean value equal to 26 pS. Finally, a voltage-and Ca2+-dependent K+ channel with a unitary conductance of 95 pS was recorded. Both the channel's amplitude and kinetics were unaffected by phenytoin. These results confirm the phenytoin effect on K+ currents and suggest that the drug may be considered a selective blocker of delayed rectifier K+ channels.