Mechanisms of Intercellular Propagation of Calcium Waves

描述(由申请人提供)：本研究的目标是确定细胞间通讯在完整心脏细胞内钙瞬变传播中的作用。当单个心肌细胞去极化时，发生机电耦合，导致钙瞬变，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过程中，钙离子通过缝隙连接通道在心肌细胞之间扩散是正常钙波传播和动力学所必需的。对对照和缝隙连接缺陷(即Cx43缺乏)心脏的钙瞬变和电压的高速成像将使我们能够阐明细胞间耦合在确定动作电位和瞬变之间的时间和空间关系中的作用。细胞内钙循环的变化已知发生在心脏发育期间和许多形式的心脏病中；我们认为细胞间耦合的生理或病理变化可能有助于这些功能变化。

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.