Effects of phenytoin on the persistent Na+ current of mammalian CNS neurones.
Whole-cell recordings in voltage-clamp mode were performed on acutely isolated neurones from rat neocortex and neostriatum to examine the effects of the anticonvulsant phenytoin on a non-inactivating (persistent) Na+ current (INaP). INaP was chosen because it enhances neuronal excitability near firing threshold, which makes it a potential target for anticonvulsant drugs. In both preparations, phenytoin (10-100 microM) inhibited INaP in a dose-dependent fashion without altering the voltage-dependence of current activation. On average, half-block of INaP was produced by 34 microM phenytoin suggesting that therapeutic drug concentrations are likely to affect INaP. Inhibition of INaP might represent a novel mechanism contributing to the anticonvulsant profile of phenytoin.
Chao
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TI
Department of Physiology, University of Munich, Germany.
Alzheimer
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C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D016015:Logistic Models; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*
D000927:Anticonvulsants; D015222:Sodium Channels; D010672:Phenytoin