ATRIAL PACEMAKER COMPLEX--ATRIAL FLUTTER & FIBRILLATION

描述(改编自申请人的摘要)：长期 这项提案的目标是揭示在 自发过程中记录事件的细胞和微观水平 在宏观水平上观察到的脉冲激发和传导 窦房结和心房图。这些研究旨在揭示 根据多中心或脉冲起因与变化之间的联系 老年人复杂的心房激动和心率变化的模式 Sa-Node准备。此外，来自SA节点的传导是 非统一和冲动只能在有限数量的站点上存在 存在结房连接。这些研究的中心是 250个细胞外和细胞内电位的同步记录 离体灌流心房微电极起搏电位的研究 准备工作。其他研究将检查细胞的形态和 全细胞电压钳起搏细胞的电生理学研究 技术，重点放在以前没有特征的起搏器细胞上 独特的蜘蛛样形态和离子通道活性，这可能是 占优势的起搏器细胞类型。这些细胞的一个有趣的方面是 可能服务于细胞间调节的长树突状突起 和沟通功能，影响细胞群体行为。此外， 从最早的细胞内起搏器区域到 通过将电生理数据与 窦房结及其周围心房的三维重建 具有重要功能的特定区域的组织。其他研究将集中在 细胞间隙连接蛋白亚型差异的研究 心房起搏器复合体(APMC)细胞之间的相互连接。人类 研究将涉及体外灌流的心房，其中细胞内， 将获得全细胞和胞外电位，并将其与 分离的窦房结起搏细胞的形态资料和研究。

DESCRIPTION (adapted from the applicant's abstract): The long-term objectives of this proposal are to reveal mechanisms operating at the cellular and microscopic level for events recorded during spontaneous impulse initiation and conduction observed at the macroscopic level in sinoatrial node and atrial maps. The studies are designed to reveal the basis for the multicentric or impulse origin and the link between changing patterns of complex atrial activation and changing heart rate in the SA-nodal preparation. Further, that conduction from the SA-node is non-uniform and impulses can only exit at a limited number of sites where there are nodal-atrial connections. The studies center about the simultaneous recordings of 250 extracellular potentials and intracellular pacemaker potentials from microelectrodes in an isolated perfused atrial preparation. Other studies will examine the morphology and cellular electrophysiology of pacemaker cells using whole-cell voltage-clamp techniques, focusing on a previously uncharacterized pacemaker cell with unique spider-like morphology and ion channel activity, which may be the dominant pacemaker cell type. An interesting aspect of these cells are the long dendritic-like projections which may serve an intercellular regulatory and communication function, affecting cell group behavior. In addition, the pathway of impulses from the earliest intracellular pacemaker region into the atrium will be determined by correlating electrophysiologic data with three dimensional reconstructions of the sinus node and surrounding atrial tissue at selected areas of functional importance. Other studies will focus on the difference in connexin protein subtypes associated with interconnections among the atrial pacemaker complex (APMC) cells. Human studies will involve in vitro perfused atria in which intracellular, whole-cell and extracellular potentials will be obtained and correlated with morphologic data and studies of isolated SA-node pacemaker cells.