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Inhibition of delayed rectifier K + channels by phenytoin in rat neuroblastoma cells
Author(s) -
Nobile Mario,
Vercellino Paolo
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700969
Subject(s) - phenytoin , depolarization , anticonvulsant , chemistry , patch clamp , neuroblastoma , biophysics , electrophysiology , inhibitory postsynaptic potential , potassium channel blocker , potassium channel , pharmacology , endocrinology , medicine , cell culture , biology , neuroscience , epilepsy , genetics
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.