Sodium channels from human brain RNA expressed in Xenopus oocytes. Basic electrophysiologic characteristics and their modification by diphenylhydantoin.
We describe the expression and characterization of sodium channels from human brain RNA in the Xenopus oocyte. The expressed channel, studied by whole-cell voltage clamp, reveals characteristic selectivity for sodium as the permeant ion, voltage-dependent gating, and block by nanomolar concentrations of tetrodotoxin. Such channels are not seen in control oocytes injected with solvent only. The anticonvulsant diphenylhydantoin (DPH) inhibits the expressed channel in a voltage- and use-dependent manner, much like the effect seen in primary mammalian neuronal preparations. The inhibition of the expressed human sodium channel by DPH can be described by models previously developed to explain block of Na channels by local anesthetics. The preferential block of Na channels during depolarization helps explain the selectivity of DPH for neurons involved in seizure activity.
Tomaselli
G F
GF
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Marban
E
E
Yellen
G
G
D000818:Animals; D001921:Brain / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010672:Phenytoin / Q000494:pharmacology*; D012313:RNA / Q000008:administration & dosage* / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin; D014981:Xenopus
D015222:Sodium Channels; D013779:Tetrodotoxin; D010672:Phenytoin; D012313:RNA