Mechanisms of Intercellular Propagation of Calcium Waves

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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.