COMPARATIVE ASPECTS OF IONIC CONDUCTANCES IN NERVE AND HEART CELL MEMBRANES

本课题是关于离子电流的比较分析 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，已经使用的主要实验制剂是 乌贼巨大的轴突 利多卡因及其衍生物对大鼠脑组织的影响 钠离子电流I-Na和钾离子电流I-K， 研究了 利多卡因阻断I-K的机制不同于 其阻断I-Na的机制。 封锁两种渠道 在药物穿过膜后， 膜的脂质部分。 然而，钠通道门必须 在利多卡因分子能够到达其阻塞部位之前打开 钾离子通道，而钾离子通道可以被阻断，无论是否 它的大门是否敞开。 这一结果表明， 当钾离子通道被药物分子吸收时， 无论是在其打开状态还是其关闭状态， 当钠通道关闭时，药物不能进入钠通道。 状态 I-K和I-Na的这种比较分析一般来说是有效的， 大多数药物 一个例外是QX 572，一种利多卡因的季铵衍生物。 钾离子通道的闸门必须打开，就像钠离子通道的情况一样。 通道，然后才能被该药物阻断。 QX 572分子是 大约是利多卡因分子的两倍长，这表明 药物分子的长度决定了钾离子通道 必须在通道阻塞发生之前打开。

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.