Anticonvulsant phenytoin affects voltage-gated potassium currents in cerebellar granule cells.
The anticonvulsant drug phenytoin (diphenylhydantoin, DPH) was examined for its action on potassium currents in cerebellar granule cells using the whole-cell patch-clamp technique. Granular cells expressed two main types of voltage-dependent potassium currents: the first, sensitive to Tetraethylammonium ion (TEA), resembles a delayed rectifier K(+) channel (I(d)); the second shows biophysical and pharmacological properties similar to an I(A)-type potassium current. Phenytoin blocks the I(A) current in a dose-dependent manner, with an apparent dissociation constant K(d) of (73+/-7) microM. The drug shifts the steady-state inactivation curves towards a more negative potential, stabilizing the inactivated state, while the activation kinetics remain unaffected. The estimated K(d) when the cell is held to -100 mV (closed state of the channel) is 145+/-8 microM which decreases to 35+/-10 microM at -80 mV holding potential (partial inactivation of the channel). Phenytoin shows a discriminant behaviour between the two different types of potassium channels because at high concentration the effect of the drug on the delayed rectifier K(+) channel is negligible.
Pisciotta
Marzia
M
Dipart. di Ingegneria Biofisica ed Elettronica, Università di Genova, Via Opera Pia 16a, Genoa, Italy.
Prestipino
Gianfranco
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004594:Electrophysiology; D010672:Phenytoin / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D024642:Potassium Channels, Voltage-Gated; D010672:Phenytoin