Mechanisms of Intercellular Propagation of Calcium Waves

描述（由申请人提供）：本研究的目标是确定完整心脏中细胞间通讯在细胞内钙瞬态传播中的作用。机电耦合发生在单个心肌细胞去极化时，导致钙瞬态导致收缩蛋白的激活。我们将测试的总体假设是，在触发钙释放和再摄取期间，肌细胞之间通过间隙连接通道的Ca2+离子扩散是正常钙波传播和动力学所必需的。控制和间隙连接缺陷（即cx43缺陷）心脏的钙瞬态和电压的高速成像将使我们能够阐明细胞间耦合在决定动作电位和瞬态之间的时空关系中的作用。已知细胞Ca2+循环的变化在心脏发育期间和许多形式的心脏病中都发生；我们认为细胞间偶联的生理或病理变化可能导致这些功能改变。

DESCRIPTION (provided by applicant): The goal of the studies proposed in this fellowship is to define the role of intercellular communication in the propagation of intracellular calcium transients in the intact heart. Electromechanical coupling occurs when individual cardiac myocytes are depolarized, leading to a calcium transient resulting in the activation of contractile proteins. The overall hypothesis that we will test is that diffusion of Ca2+ ions between myocytes through gap junction channels during triggered calcium release and reuptake is required for normal calcium wave propagation and dynamics. High speed imaging of calcium transients and voltage in control and gap junction deficient (i.e., Cx43-deficient) hearts will enable us to elucidate the role of intercellular coupling in determining the temporal and spatial relationships between the action potential and transients. Changes in cellular Ca2+ cycling are known to occur both during heart development and in many forms of heart disease; we propose that physiological or pathologic changes in intercellular coupling may contribute to these functional alterations.