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: 3969016
• 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/3969016
• 关键词: action potentials; antiarrhythmic agent; axon; cell membrane; computer simulation; drug metabolism; embryo /fetus cell /tissue; glia; heart cell; heart pharmacology; ion transport; lidocaine; mathematical model; membrane permeability; membrane potentials; neurons; neurophysiology; saltwater environment; single cell analysis; tetraethylammonium compound; tetrodotoxin

This project is concerned with a comparative analysis of ionic current channels in nerve and heart cell membranes and the relationship of these channels to electrical activity, with a particular emphasis on potassium ion channels in both preparations and the effects of various ionic blockers on these channels. During the past year the primary experimental preparations which have been used are squid giant axons, chick embryonic heart cells, and mongrel dog hearts. The mechanisms by which ionic blockers and other agents alter potassium ion currents in the squid and chick heart cell preparations have been investigated with the voltage clamp technique. This work has focused recently on the derivatives of triethylammonium ions. A major finding has been the discovery of a relationship between the size of the ionic blocker and the mechanism of blockade. Specifically, the smaller sized members of this sequence, such as methyltriethylammonium and tetraethylammonium block channels without altering channel gating, whereas blockage by larger sized ions, such as n-pentyltriethylammonium and n-nonyltriethylammonium is accompanied by an alteration of gating. The relationship between potassium channel blockade and the mechanism of anti-fibrillatory drugs has been further investigated with the open-chested dog heart preparation using quaternary derivatives of lidocaine. In particular, QX314 and QX572 produce a significant increase in ventricular fibrillation threshold, which is well correlated with the blockade of potassium current in the squid and chick heart cell preparations which these agents produce. The relationship between ionic currents and spontaneous electrical activity in the heart has been further investigated with our ionic current model of embryonic chick atrial cells. Addition of 10-8M tetrodotoxin alters the shape of the action potential without altering beat rate. An analysis of our measurements of sodium ion current, I-Na, from single cells using the suction pipette technique before and after application of TTX, together with our computer model, illustrates the role of I-Na in spontaneous activity.

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以及它们之间的关系 电活动的通道，特别强调钾 两种制剂中的离子通道和各种离子阻断剂的作用 在这些频道上。 在过去的一年里，主要的实验 已经使用的制剂是鱿鱼巨轴突、鸡胚 心脏细胞和杂种狗的心脏。 离子的机制 阻断剂和其他药剂改变鱿鱼中的钾离子电流， 用电压钳研究了鸡心肌细胞的制备 法 这项工作最近集中在衍生物的 三乙基铵离子。 一个主要的发现是， 离子阻断剂的大小与 封锁 具体地说，这个序列中较小的成员，如 因为甲基三乙基铵和四乙基铵阻断通道， 改变通道门控，而较大尺寸的离子，如 正戊基三乙基铵和正壬基三乙基铵伴随有 门控的改变。 钾通道阻滞剂与 并对其作用机制进行了深入研究 对于开胸狗心脏制剂， 利多卡因 特别是QX 314和QX 572， 室颤阈值，这与 鱿鱼和鸡心肌细胞钾电流的阻断 这些制剂生产的。 离子之间的关系 心脏的电流和自发电活动已经进一步 用我们的鸡胚心房细胞离子电流模型研究。 加入10- 8 M河豚毒素改变动作电位的形状 而不改变心跳速率。 钠离子测量结果分析 电流，I-Na，从单细胞使用吸管技术之前， 应用TTX后，结合我们的计算机模型， I-Na在自发活动中的作用。