COMPARATIVE ASPECTS OF IONIC CONDUCTANCES IN NERVE AND HEART CELL MEMBRANES

神经细胞和心脏细胞膜中离子电导的比较

• 批准号: 4696937
• 负责人: J R CLAY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696937
• 关键词: action potentials; antiarrhythmic agent; axon; cell membrane; drug metabolism; embryo /fetus cell /tissue; glia; heart cell; heart pharmacology; lidocaine; mathematical model; membrane permeability; membrane potentials; neurons; neurophysiology; potassium; saltwater environment

This project is concerned with a comparative analysis of ionic current channels in nerve and heart cell membranes with a particular emphasis on the effects of cardioactive drugs on both preparations. During the past year the primary experimental preparation which has been used has been the squid giant axon. The effects of lidocaine and its derivatives on the sodium ion current, I-Na, and the potassium ion current, I-K, have been studied. The mechanism by which lidocaine blocks I-K is different from the mechanism by which it blocks I-Na. Blockade of both types of channels occurs on the interior surface of the membrane, after the drug has crossed the lipid portion of the membrane. However, the sodium channel gates must open before a lidocaine molecule can reach its blocking site within the channel, whereas a potassium channel can be blocked regardless of whether or not its gates are open. This result suggests that the inner mouth of the potassium channel is accessible to drug molecules when the channel is either in its open or its closed state, whereas the inner mouth of the sodium channel is not accessible to drugs when the channel is in its closed state. This comparative analysis of I-K and I-Na is valid, in general, for most drugs. One exception is QX572, a quaternary derivative of lidocaine. The potassium channel gates must open, as is the case with the sodium channel, before blockade by this drug can occur. The QX572 molecule is about twice as long as the lidocaine molecule, which suggests that the length of a drug molecule determines whether or not a potassium channel must open before channel blockade can occur.

该项目涉及对离子流的比较分析。 神经和心脏细胞膜中的通道，特别强调 心脏活性药物对两种制剂的影响。在过去 一年来，使用的主要实验制剂是 乌贼巨型轴突。利多卡因及其衍生物对小鼠心脏功能的影响 钠离子电流I-Na和钾离子电流I-K 学习。利多卡因阻断I-K的机制不同于 它阻断I-Na的机制。封锁这两类渠道 在药物交叉后，发生在膜的内表面 膜的脂类部分。然而，钠通道门必须 在利多卡因分子到达其封闭位置之前打开 通道，而钾通道可以被阻断，无论是否 否则，它的大门就会敞开。这一结果表明，人的内口 当钾通道被药物分子访问时，该通道是可被药物分子访问的 处于打开或关闭状态，而 当钠通道处于关闭状态时，药物不能进入该通道 州政府。I-K和I-Na的这种比较分析一般适用于 大多数毒品。一个例外是QX572，利多卡因的四元衍生物。 钾通道门必须打开，就像钠一样 渠道，在这种药物可能发生封锁之前。QX572分子是 大约是利多卡因分子的两倍，这表明 药物分子的长度决定了钾通道是否 必须在通道阻塞发生之前打开。