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Nicotine depresses the functions of multiple cardiac potassium channels.

机译:尼古丁会降低多个心脏钾通道的功能。

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Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.
机译:尼古丁是烟草烟雾的主要成分,可能与引发吸烟相关的心血管疾病和与吸烟相关的突然冠状动脉死亡,可能是由于引发心律不齐。细胞机制可能与尼古丁延长动作电位和使膜电位去极化的能力有关。然而,潜在的离子机制仍然未知。我们在这里显示尼古丁阻断了多种类型的K +电流,包括犬心室肌细胞中的天然电流以及非洲爪蟾卵母细胞中表达的克隆通道:A型K +电流(I(to)/Kv4.3),延迟整流K +电流( I(Kr)/ HERG)和内向整流器K +电流(I(K1)/Kir2.1)。最引人注意的是,浓度低至10 nM的尼古丁可将I(to)和Kv4.3抑制约20%。尼古丁的作用与烟碱样受体模拟或儿茶酚胺释放无关。我们的结果表明,尼古丁是K +通道的非特异性阻断剂,其抑制作用是尼古丁分子与通道蛋白之间直接相互作用的结果。我们的研究首次为尼古丁直接抑制心脏K +通道提供了证据,并建立了尼古丁药理学的一个新方面。

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