ELECTROPHYSIOLOGY OF RIGHT ARTIAL SUBSIDIARY PACEMAKERS

本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，并比较这些 与主（SA结）起搏器相同的发现 物种 本研究中使用的方法将涉及记录电压和 从咽鼓管分离的单个起搏细胞的离子电流 猫右心房的脊和SA结。 将通过以下方法分离细胞： 用酶逆行（Langendorf）灌注整个心脏 （胶原酶）溶液。 将使用单次抽吸记录信号 玻璃移液管在整个细胞配置。 单细胞将是 使用不连续电压箝位方法箝位的电压和Pclamp 软件程序。 单细胞的形态将使用 电子显微镜技术。 这项研究的具体目标将包括一系列 实验来确定离子电流机制负责 辅助起搏自律性 这将涉及电压钳位 分析i-f起搏电流、iK钾电流、T-和 L型慢内向钙电流和漏电流。 第二系列 实验将确定离子电流机制负责 辅助起搏器对肾上腺素能、胆碱能、嘌呤能的反应 和肽能受体刺激。 这将包括一个电压钳 离子电流变化的分析， 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）。 第三个系列的实验将确定 离子电流机制负责的影响，改变， 钾、钙和镁离子浓度。 在适当的情况下， 离子组成的细胞内和细胞外变化都将是 分析了 本研究的第四个目的是确定 心房附属起搏细胞的超微结构特征。 最后，心房辅助起搏器的发现（如上所述） 将bc与主（SA结）起搏器中发现的相比。 在这 这些实验将直接比较电生理学， 次级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 目前，对细胞机制知之甚少， 控制或调节心房辅助起搏器活动的机制， 在不正常的情况下，因素会发生变化。 这一信息至关重要 了解正常和异常心房功能。 这些 实验将提供新的信息，以更好地了解 控制和调节心房起搏的基本机制 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.