Contraction of the heart occurs by the intracellular release of calcium through channels called ryanodine receptors (RyR), after electrical activation. Due to the progression of heart disease, structural and functional remodeling of at the level of the cardiac cell is known to occur. This remodeling process alters the electrical properties of the heart muscle cell and can lead to the production of an irregularity in the electrical activity of the heart called an arrhythmia. Studies have shown a that disruption of the normal behavior of the RyR can lead to the production of arrhythmic events and these have been linked to the occurrence of intracellular waves of propagating calcium release called calcium waves. The precise mechanisms which underlie this process are currently unknown and warrant further investigation. Using a multidisciplinary approach, alterations in RyR cluster structure will be assessed and correlated with alterations in calcium release after remodeling in a rabbit model of myocardial infarction. Using cultured rabbit myocytes, the involvement of a protein called junctophilin-2 in the regulation of the RyR clustering process will also be assessed. The functional consequences of RyR cluster morphological alteration will be assessed, such as phosphyorylation and the efficacy of anti-arrhythmic drugs.
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