CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS & DRUGS

在过去的十年里，我们对心脏病的认识有了真正的爆炸性增长。 膜电导，主要是由于获得健康的能力， 分离的心肌细胞。 这些新的信息大部分是从 心室和心房肌细胞，因为他们很容易， 是分离的。 相比之下， 浦肯野肌细胞，虽然检查其性质是核心， 了解许多危及生命的心律失常的起源。 我们的实验室已经开发出一种可靠的技术， 浦肯野肌细胞从他们的胶原基质。 我们研究 分离的浦肯野肌细胞的电生理特性， 浦肯野纤维的 在本申请中，我们提出继续我们的三个方面的研究。 浦肯野细胞膜电流：内向整流电流iK 1， 一系列重要问题的答案。 关于iK 1， 问题包括起源或整改，内部发挥的作用， K在门控iK 1，和控制失活的这种电导， B刺激。 我们对起搏器电流的研究将集中在 我们最近发现乙酰胆碱可以逆转B激动剂对If的作用， 而不会产生直接的影响。 我们还将调查 起搏器激活延迟的起源。 我们对钠钾泵的研究 目前将试图阐明一个数量级的原因， 二氢哇巴因抑制Na/K泵能力的差异 心室肌细胞与浦肯野肌细胞的电流。 第二组 实验检查Na/K泵与Na/Ca的相互作用 交换器响应于钙负荷，或响应于长时间的 强心苷对钠/钾泵的阻断。 这些研究应该为我们提供了重要的见解， 浦肯野肌细胞的电生理学和药理学， 正常功能可以修改。

The past decade has seen a veritable explosion in our knowledge of cardiac membrane conductances, largely due to the ability to obtain healthy isolated cardiac myocytes. Most of this new information has been obtained from ventricular and atrial myocytes because of the ease with which they are dissociated. In contrast much less progress has been made on the Purkinje myocyte although examining its properties is central to understanding the origin of many life threatening arrhythmias. Our laboratory has developed a reliable technique for the dissociation of Purkinje myocytes from their collagenous matrix. We study the electrophysiologic properties of the isolated Purkinje myocytes and also those of the Purkinje fibers. In the present application we propose to continue our studies of three Purkinje membrane currents: the inward rectifier current iK1, the pacemaker to a number of important questions. With respect to iK1 these questions include the origin or rectification, the role played by internal K in gating iK1, and the control of the inactivation of this conductance by B stimulation. Our investigations of the pacemaker current will center on our recent finding that acetylcholine can reverse B agonist effects on if without having direct effects of its own. We will also investigate the origin of the pacemaker activation delay. Our studies of the Na/K pump current will attempt to elucidate the reasons for an order of magnitude difference in the ability of dihydroouabain to inhibit the Na/K pump current in ventricular versus Purkinje myocytes. A second set of experiments examines the interaction of the Na/K pump with the Na/Ca exchanger in response to a calcium load, or in response to prolonged blockade of the Na/K pump by cardiac glycosides. These studies should provide us with important insights into the normal electrophysiology and pharmacology of the Purkinje myocyte, and how this normal function can be modified.