Microdomein interacties tussen de intracellulaire Ca kanalen IP3R and RyR na myocard infarct

Dysregulation of Ca2+ regulatory mechanisms results in pathological changes in cardiac function precipitating arrhythmia and reduced contractility. Central to the generation of Ca2+ signals in the heart is the ryanodine receptor (RyR) intracellular Ca2+ release channel. Release of Ca2+ by this channel is modified during disease, contributing to pathlogy. Albeit at a lower abundance, cardiac myocytes also express IP3 regulated intracellular channels (IP3Rs). The expression of these channels is increased during disease and owing to the enhanced GCPR signalling, also associated with pathology, their contribution to cardiomyocyte Ca2+ regulation is increased. In particular, by modulating Ca2+ release via co-localised RyRs, IP3R signalling results in alterations in contractility and promotes arrhythmia. Here we will investigate the crosstalk between these two Ca2+ release channels in cardiac myocytes. By studying these interactions in a large mammal post myocardial infarction preclinical model of disease we will determine whether enhanced IP3R signalling is an adaptive repsonse of the cardiac myocyte to enhance RyR activity thereby mitigating against the disruption in RyR mediated Ca2+ signalling and it induction of contraction during disease.