Tomaselli G F, Marban E, Yellen G
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
J Clin Invest. 1989 May;83(5):1724-32. doi: 10.1172/JCI114073.
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.
我们描述了从人脑中提取的RNA在非洲爪蟾卵母细胞中表达的钠通道及其特性。通过全细胞膜片钳技术研究该表达通道,发现其对通透离子钠具有特征性选择性、电压依赖性门控以及被纳摩尔浓度的河豚毒素阻断。在仅注射溶剂的对照卵母细胞中未观察到此类通道。抗惊厥药苯妥英(DPH)以电压和使用依赖性方式抑制该表达通道,这与在原代哺乳动物神经元制剂中观察到的效应非常相似。DPH对所表达的人钠通道的抑制作用可用先前开发的用于解释局部麻醉药对钠通道阻断作用的模型来描述。去极化过程中钠通道的优先阻断有助于解释DPH对参与癫痫活动神经元的选择性。