CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS AND DRUGS

心脏浦肯野链是一个合胞体。 任何观察到的性质 合胞体依赖于膜的渗透性和 膜电流随细胞外几何形状流动。 本 赠款提案建立在前五年的研究基础上， 用各种技术研究了犬心脏浦肯野束，包括 形态计量学分析，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， 表征细胞膜的性质，如被细胞膜扭曲的性质。 细胞外间隙 这项拨款的其中一个主要目的， 类似电压钳和阻抗分析的一种新的编制方法， 急性分离的犬心脏浦肯野肌细胞。 希望A 详细的电压钳分析， 应该提供必要的缺失环节，使我们能够准确地 从完整的浦肯野束中解读我们的数据 拟议的研究 解离的细胞包括分析平台期和舒张期 延迟整流器，Na/K泵电流的表征，以及 研究各种药物对稳定的 说明电流-电压关系。 第二个目标是继续我们的分析， 合胞体制备物中的各种膜电流。 这些电流 包括由一段时间的快速活动引发的Na/K泵电流， 缓慢失活TTX敏感的“窗口电流”， 舒张延迟整流器。 一些拟议的实验采用 在电压钳下同时测量两个膜电流 和胞外[K]。 这应该提供更多的洞察力， 在时间依赖的解释中裂缝[K]变化的重要性 膜电流 希望这些实验将增加我们的 了解动作电位持续时间的控制， 正常和病理条件下的起搏器活动。

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.