ELECTROPHYSIOLOGY OF RIGHT ARTIAL SUBSIDIARY PACEMAKERS

这项研究项目的长期目标是确定 电生理机制、功能特性和形态 心房辅助起搏器的特点，并进行比较 在同一起搏器的初级(SA节点)起搏器中的发现 物种。 这项研究中使用的方法将涉及记录电压和 咽鼓管单个起搏细胞的离子电流 猫右心房的隆起和窦房结。细胞将被分离出来 全心逆行(朗恩多夫)酶灌注术 (胶原酶)溶液。信号将使用一次吸力进行记录 玻璃吸管在整个电池配置中。单个单元格将是 使用不连续电压钳位方法和钳位的电压钳位 软件程序。单个细胞的形态将用 电子显微镜技术。 这项研究的具体目标将包括一系列 确定离子电流机制的实验 自动辅助起搏器。这将涉及一个电压钳位 I-f起搏器电流、Ik钾电流、T-和 L型慢内向钙电流和漏电流。第二个系列 实验将确定离子电流机制负责 副起搏器对肾上腺素能、胆碱能、嘌呤能的反应 和肽能受体的刺激。这将包括一个电压钳位 离子电流响应的变化分析 异丙肾上腺素、甲氧胺、乙酰胆碱、腺苷和降钙素基因 相关肽(CGRP)。第三系列实验将确定 离子流机制负责的变化的影响 钾、钙、镁离子浓度。在适当情况下， 细胞内和细胞外离子组成的变化都将是 分析过了。这项研究的第四个目标是确定形态 心房辅助起搏细胞的超微结构特征。 最后，在心房辅助起搏器中的发现(如上所述) 将Bc值与初级(SA结)起搏器中发现的Bc值进行比较。在这 方式，这些实验将直接比较电生理学， 附属起搏细胞与初级起搏细胞的功能和形态 从同一物种的心脏中分离出来的。 目前，人们对细胞机制知之甚少。 管理或调节心房辅助起搏器的活动，或者这些 在不正常的情况下，因素会发生变化。这些信息是必不可少的 以了解正常和异常的心房功能。这些 实验将提供新的信息，有助于更好地理解 控制和调节心房起搏器的基本机制 活动。

The long range objective of this research project is to determine the electrophysiological mechanisms, functional properties and morphological characteristics of atrial subsidiary pacemakers, and to compare these findings to those found in primary (SA node) pacemakers of the same species. The methods used in this study will involve recording voltage and ionic currents from single pacemaker cells isolated from the eustachian ridge and SA node of the cat right atrium. Cells will be isolated by retrograde (Langendorf) perfusion of the whole heart with enzyme (collagenase) solutions. Signals will be recorded using a single suction glass pipette in the whole cell configuration. Single cells will be voltage clamped using a discontinuous voltage clamp method and Pclamp software programs. The morphology of single cells will be determined using electron microscopic techniques. The specific aims of this study will include a series of experiments to determine the ionic current mechanisms responsible for subsidiary pacemaker automaticity. This will involve a voltage clamp analysis of the i-f pacemaker current, the iK potassium current, the T- and L-type slow inward Ca 2+ currents and leak currents. A second series of experiment will determine the ionic current mechanisms responsible for the response of subsidiary pacemakers to adrenergic, cholinergic, purinergic and peptidergic receptor stimulation. This will include a voltage clamp analysis of the ionic current changes that occur in response to isoproterenol, methoxamine, acetylcholine, adenosine and calcitonin gene related peptide (CGRP). A third series of experiments will determine the ionic current mechanisms responsible for the effects of alterations in potassium, calcium and magnesium ion concentrations. Where appropriate, both intracellular and extracellular changes in ionic composition will be analyzed. A fourth aim of this research is to determine the morphological (ultrastructural) characteristics of atrial subsidiary pacemaker cells. Finally, the findings in atrial subsidiary pacemakers (as described above) will bc compared with those found in primary (SA node) pacemakers. In this way, these experiments will directly compare the electrophysiology, function and morphology of subsidiary versus primary pacemaker cells isolated from hearts of the same species. At present, there is little known about the cellular mechanisms that govern or regulate atrial subsidiary pacemaker activity or how these factors change under abnormal conditions. This information is essential for an understanding of normal and abnormal atrial f unction. These experiments will provide new information toward a better understanding of the fundamental mechanisms that control and regulate atrial pacemaker activity.