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利多卡因对移植到非洲爪蟾卵母细胞中的 Torpedo 烟碱型乙酰胆碱受体的多种抑制作用。

Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes.

机构信息

División de Fisiología, Dpto. de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain.

出版信息

J Neurochem. 2011 Jun;117(6):1009-19. doi: 10.1111/j.1471-4159.2011.07271.x. Epub 2011 May 10.

Abstract

Lidocaine is a local anaesthetic that blocks sodium channels, but also inhibits several ligand-gated ion-channels. The aim of this work was to unravel the mechanisms by which lidocaine blocks Torpedo nicotinic receptors transplanted to Xenopus oocytes. Acetylcholine-elicited currents were reversibly blocked by lidocaine, in a concentration dependent manner. At doses lower than the IC(50) , lidocaine blocked nicotinic receptors only at negative potentials, indicating an open-channel blockade; the binding site within the channel was at about 30% of the way through the electrical field across the membrane. In the presence of higher lidocaine doses, nicotinic receptors were blocked both at positive and negative potentials, acetylcholine dose-response curve shifted to the right and lidocaine pre-application, before its co-application with acetylcholine, enhanced the current inhibition, indicating all together that lidocaine also blocked resting receptors; besides, it increased the current decay rate. When lidocaine, at low doses, was co-applied with 2-(triethylammonio)-N-(2,6-dimethylphenyl) acetamide bromide, edrophonium or 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide, which are quaternary-ammonium molecules that also blocked nicotinic receptors, there was an additive inhibitory effect, indicating that these molecules bound to different sites within the channel pore. These results prove that lidocaine blocks nicotinic receptors by several independent mechanisms and evidence the diverse and complex modulation of this receptor by structurally related molecules.

摘要

利多卡因是一种局部麻醉剂,可阻断钠离子通道,但也可抑制几种配体门控离子通道。本工作旨在揭示利多卡因阻止移植到非洲爪蟾卵母细胞中的 Torpedo 烟碱型乙酰胆碱受体的机制。乙酰胆碱诱发的电流可被利多卡因可逆地阻断,且具有浓度依赖性。在低于 IC50 的剂量下,利多卡因仅在负电位下阻断烟碱型受体,表明是通道开放阻断;通道内的结合位点大约在膜电场的 30%处。在存在较高剂量的利多卡因时,烟碱型受体在正、负电位下均被阻断,乙酰胆碱剂量-反应曲线右移,并且在与乙酰胆碱共同应用之前,预先应用利多卡因可增强电流抑制,表明利多卡因还可阻断静息受体;此外,它还增加了电流衰减速率。当低剂量的利多卡因与 2-(三乙铵)-N-(2,6-二甲基苯基)乙酰胺溴化物、依酚氯铵或 1,5-双(4-烯丙基二甲铵基苯基)戊烷-3-酮二溴化物共同应用时,这些都是可阻断烟碱型受体的季铵分子,会产生附加抑制作用,表明这些分子结合到通道孔内的不同位点。这些结果证明利多卡因通过多种独立的机制阻断烟碱型受体,并证明了结构相关分子对该受体的多样化和复杂调节。

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