CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS AND DRUGS

心脏浦肯野链是一种合胞体。任何可观察到的属性 合胞体既依赖于膜的通透性，也依赖于 膜电流随细胞外几何形状流动。现在 赠款提案建立在之前五年的研究基础上，在这些研究中， 用多种技术研究犬心脏浦肯野链，包括 形态分析、电压钳、细胞外离子选择性 微电极和阻抗分析。从这些研究中，我们得到了一个 被扭曲的细胞膜的特性的表征 细胞外空间。目前拨款的一个主要目的是提供 一种新制剂的相似电压钳和阻抗分析 急性分离的犬心脏浦肯野肌细胞。希望能有一个 合并体的这块积木的详细电压钳位分析 应该提供必要的缺失环节，使我们能够准确地 从完整的浦肯野链解读我们的数据。建议进行的研究 分离的细胞包括平台和舒张期的分析。 延迟整流，Na/K泵电流的特性，以及 不同药理药物对药物稳定性影响的研究 说明电流-电压关系。 目前拨款建议的第二个目的是继续分析 合胞体准备过程中的各种膜电流。这些洋流 包括由一段时间的快速活动启动的Na/K泵电流， 缓慢地使TTX敏感的“窗口电流”失活，并且平台和 舒张期延迟整流仪。一些拟议的实验采用了 电压钳下两种膜电流的同时测量 和胞外[K]。这应该会为我们提供对 裂隙[K]变化在时间依赖性解释中的重要性 膜电流。 希望这些实验将增加我们的 了解对动作电位时程的控制，以及 起搏器在正常和病理条件下的活动。

The cardiac Purkinje strand is a syncytium. The observed properties of any syncytium depend on both the membrane permeabilities and the interaction of the membrane current flows with the extracellular geometry. The present grant proposal builds on the previous five years of research in which the canine cardiac Purkinje strand was studied by various techniques including morphometric analysis, voltage clamp, extracellular ion selective microelectrodes, and impedance analysis. From these studies we have a characterization of the properties of the cell membrane as distorted by the extracellular space. One major aim of the present grant is to provide similar voltage clamp and impedance analysis of a new preparation, the acutely isolated canine cardiac Purkinje myocyte. It is hoped that a detailed voltage clamp analysis of this building block of the syncytium should provide the necessary missing link to allow us to accurately interpret our data from the intact Purkinje strands. Proposed studies of the dissociated cells include analysis of both plateau and diastolic delayed rectifiers, characterization of the Na/K pump current, and investigation of the effects of various pharmacologic agents on the steady state current-voltage relationship. A second aim of the present grant proposal is to continue our analysis of various membrane currents in the syncytial preparation. These currents include the Na/K pump current initiated by a period of rapid activity, the slowly inactivating TTX-sensitive "window current" and both plateau and diastolic delayed rectifiers. Some of the proposed experiments employ simultaneous measurements of both the membrane currents under voltage clamp and the extracellular [K]. This should provide additional insight into the importance of changes in cleft [K] in the interpretation of time dependent membrane currents. It is hoped that these experiments will provide an increase in our understanding of the control of both the action potential duration, and pacemaker activity in normal and pathologic conditions.