ACTION OF ADENOSINE ON NODAL AND ATRIAL CELLS

我们以前的工作表明，a)腺苷导致窦性心动过缓和 房室传导阻滞(房室传导阻滞)在多种动物模型中的应用 人类，以及，b)腺苷可能参与了缺血和/或缺氧 诱发窦性心动过缓和房室传导阻滞。这次会议的主要目标是 提议定义和描述细胞机制(S) 腺苷对窦房结和房室结的作用 作为工作的心房心肌。这些实验将在 小SA节点制剂，200-300 Mum，防止起搏器移位， 单个分离的房室结细胞和房室结细胞。分离的细胞和 小SA节点是所提出的电压钳位的理想准备 学习。此外，这些研究将允许精确确定 腺苷反应的动力学。我们将使用两个微电极 用于离子电流分析的电压钳技术，离子灵敏 钾离子流出量的直接测量电极和 加压注射(细胞外应用腺苷)治疗动力学 腺苷反应的分析。我们计划使用这些技术来 描述腺苷、腺苷类似物、拮抗剂和 腺苷摄取抑制剂对所有三种细胞类型。除了……之外 提供关于细胞机制和动力学的知识 腺苷对窦房结、房室结和心房细胞的反应 将为脉冲的临床评估提供新的视角 形成和传导干扰。通过我们的多层次方法， 研究单个分离的细胞到人类，我们已经获得了一些洞察 腺苷作为心脏调节剂的潜在意义 功能。因此，目前的提案将使我们能够延长我们的 努力使用这类方法来了解该机制 腺苷在心脏中的作用。

Our previous work has shown that a) adenosine induces sinus slowing and atrioventricular (AV) block in a number of animal models and recently in humans, and, b) adenosine may be involved in the ischemia and/or hypoxia induced sinus bradycardia and AV block. The principal objectives of this proposal are to define and characterize the cellular mechanism(s) underlying the actions of adenosine on sinoatrial (SA) and AV nodes as well as the working atrial myocardium. The experiments will be conducted on small SA node preparations, 200-300 Mum, which preclude pacemaker shift, and on single isolated atrial and AV node cells. The isolated cells and small SA node are ideal preparations for the proposed voltage clamp studies. In addition, the studies will allow precise determination of the kinetics of the adenosine response. We will use the two microelectrode voltage clamp technique for ionic current analysis, ion sensitive electrodes for the direct measurement of potassium efflux and pressure-injection (adenosine applied extracellularly) for the kinetic analysis of the adenosine response. We plan to use these techniques to characterize the actions of adenosine, adenosine analogs, antagonists, and adenosine uptake inhibitors on all three cell types. In addition to providing knowledge concerning the cellular mechanism and kinetics of the response in SA node, AV node and atrial cells to adenosine, these studies will provide new perspectives in the clinical evaluation of impulse formation and conduction disturbances. Through our multi-leveled approach, studying single isolated cells to humans, we have gained some insight into the potential significance of adenosine as a modulator of cardiac function. Therefore, the present proposal will allow us to extend our efforts in using this type of approach towards understanding the mechanism of action of adenosine in the heart.