ELECTROPHYSIOLOGY OF RIGHT ATRIAL SUBSIDIARY PACEMAKERS

右心房附属起搏器的电生理学

• 批准号: 3339256
• 负责人: STEPHEN Lloyd LIPSIUS
• 金额: $ 10.61万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339256
• 关键词: acetylcholine; action potentials; atrial fibrillation; cardiac glycosides; cellular pathology; drug adverse effect; electrocardiography; electron microscopy; electrophysiology; heart function; heart pharmacology; microelectrodes; nifedipine; norepinephrine; sarcoplasmic reticulum; single cell analysis; strophanthidin; verapamil

Normally, the sinoatrial node (SA node) functions as the primary pacemaker of the heart. However, there are subsidiary pacemakers within the right atrium, outside of the SA node, that may function as a failsafe mechanism in the event of SA node dysfunction or may be responsible for generating atrial dysrhythmias. Although their importance is well recognized, little is known about subsidiary atrial pacemaker function. Therefore, the long range goal of this research is to elucidate the ultrastructural, electrophysiological and functional characteristics of subsidiary atrial pacemaker activity. Atrial tissue exhibiting subsidiary pacemaker activity is obtained from cats that are anesthetized with sodium pentobarbital (40 mg/kd; iv). Standard intracellular microelectrodes will be used to study the electrical activity and a photoelectric displacement transducer will be used to measure developed tension. To study the ionic currents responsible for subsidiary pacemaker activity, single pacemaker cells will be obtained by enzymatic dispersion and voltage clamped using single whole cell voltage clamp techniques. Finally, light and electron microscopy will be used to study the ultrastructural characteristics of subsidiary pacemaker fibers. Preliminary results indicate that subsidiary atrial pacemaker automaticity is determined primarily by calcium movements. Therefore, in section I of the proposal intracellular microelectrodes and tension recordings will be used to study the response of subsidiary pacemakers to specific pharmacological agents and interventions that alter calcium movements via 1) the slow inward current, 2) intracellular release from the sarcoplasmic reticulum, 3) sodium/calcium exchange, and 4) a calmodulin regulated process. In section II, enzyme dispersion will be used to isolate single pacemaker cells for single whole cell voltage clamp studies. The initial experiments will test the viability of the single cells. Current-voltage relations will be used to determine ionic conductance characteristics. Finally, experiments will be directed toward determining the ionic currents participating in subsidiary pacemaker automaticity. These studies will provide new and important information toward furthering our understanding of fundamental mechanisms of subsidiary pacemaker activity. In addition, they will provide new insight into mechanisms of atrial dysrhythmias.

正常情况下，窦房结（SA结）作为主要起搏器发挥作用 的心脏。 然而，右心室内有辅助起搏器， 心房，在SA结的外部，可能起到故障保护机制的作用 在SA结功能障碍的情况下，或可能导致产生 房性心律失常 虽然他们的重要性是公认的， 已知心房辅助起搏器功能。 因此，长 本研究的范围目标是阐明超微结构， 副心房电生理和功能特点 起搏器活动 显示辅助起搏活动的心房组织获自 用戊巴比妥钠（40 mg/kd; iv）麻醉的猫。 将使用标准细胞内微电极来研究电刺激。 活动和光电位移传感器将用于 测量产生的张力。 为了研究离子电流 辅助起搏活动，单个起搏细胞将通过 使用单个全细胞电压的酶分散和电压钳位 钳位技术 最后，光学和电子显微镜将用于 研究次级起搏纤维的超微结构特征。 初步结果表明，辅助心房起搏器自律性 主要由钙的运动决定。 因此，在第一节， 建议的细胞内微电极和张力记录将 用于研究辅助起搏器对特定 通过以下方式改变钙运动的药物和干预措施 1)缓慢的内向电流，2）从肌浆细胞内释放 网，3）钠/钙交换，和4）钙调蛋白调节 过程 在第二节中，酶分散将用于分离单 用于单个全细胞电压钳研究的起搏细胞。 初始 实验将测试单细胞的活力。 电流电压 关系将用于确定离子电导特性。 最后，实验将针对确定离子电流 参与辅助起搏自律性。 这些研究将 提供新的和重要的信息，以促进我们的了解 辅助起搏器活动的基本机制。 此外，本发明还提供了一种方法， 它们将为心房节律障碍的机制提供新的见解。