CARDIAC ELECTROPHYSIOLOGY--EFFECTS OF IONS AND DRUGS

在过去的十年里，我们对心脏疾病的了解出现了真正的爆炸性增长 膜电导，很大程度上是由于获得健康 分离的心肌细胞。这些新信息中的大部分都已经获得 来自心室和心房的肌细胞，因为它们很容易 是分离的。相比之下，在这方面的进展要小得多。 浦肯野肌细胞尽管检测其特性是 了解许多危及生命的心律失常的起源。 我们实验室已经开发出一种可靠的解离技术 浦肯野肌细胞从其胶原基质中分离。我们研究了 分离的浦肯野肌细胞的电生理特性 这些是浦肯野纤维。 在本申请中，我们建议继续研究三个 浦肯野膜电流：内向整流电流iK1， 起搏器回答了一些重要的问题。关于iK1这些 问题包括起源或整改，内部起到的作用 K在门控iK1中，并且通过以下方式控制该电导的失活 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IF的B受体激动剂效应 而不会产生自身的直接影响。我们还将调查 起搏器激活延迟的来源。我们对钠钾泵的研究 Current将试图阐明数量级的原因 二氢哇巴因抑制Na/K泵能力的差异 心室肌细胞电流与浦肯野肌细胞电流的比较。第二套 Na/K泵与Na/Ca相互作用的实验研究 对钙负荷的反应，或对长时间的反应 强心苷对钠钾泵的阻断作用。 这些研究应该为我们提供对常态的重要见解 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.