期刊
TOXICOLOGY IN VITRO
卷 21, 期 4, 页码 656-664出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2007.01.009
关键词
cocaine; psychostimulant; GIRK channel; Kir channel; Xenopus oocyte
类别
Cocaine, a commonly abused psychostimulant, interacts with not only transporters for dopamine, serotonin and norepinephrine but also several receptors and channels. However, the molecular mechanisms underlying the various effects of cocaine remain to be clarified. Using the Xenopus oocyte expression assay, we investigated the effects of cocaine on G protein-activated inwardly rectifying K+ (GIRK) channels, which regulate neuronal excitability and the heart rate. In oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, cocaine reversibly reduced basal GIRK inward currents. The inhibition by cocaine at the toxic levels was concentration-dependent, but voltage-independent and time-independent during each voltage pulse. However, methylphenidate, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) at their toxic concentrations had little effect on the channels. Additionally, Kirl.1 and Kir2.1 channels were insensitive to all of the drugs. The inhibition by cocaine, which exists mainly in a protonated form at pH 7.4, was not affected by extracellular pH 9, at which the proportion of the uncharged form increases, suggesting the inhibition by both forms with similar effectiveness, and at physiological pH the effect being predominantly due to the protonated cocaine. Our results suggest that inhibition of GIRK channels by cocaine may contribute to some of its toxic effects. (C) 2007 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据