Mechanisms of Intercellular Propagation of Calcium Waves

描述（由申请人提供）：本研究的目的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，从而导致收缩蛋白的激活。我们将检验的总体假设是，正常钙波传播和动力学需要在触发钙释放和再摄取期间通过间隙连接通道在肌细胞之间扩散Ca2+离子。对照和间隙连接缺陷（即，Cx43缺陷）的心脏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Ca2+循环的变化是已知的心脏发育过程中发生，并在许多形式的心脏病，我们建议，在细胞间耦合的生理或病理变化可能有助于这些功能的改变。

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.