Abstract
Cardiovascular disease is one of the leading causes of mortality in New Zealand and is responsible for one third of all global deaths each year. Among cardiac diseases, arrythmias are one of the most prevalent forms. The main mechanism of arrhythmia are inappropriate releases of Ca2+ (termed Ca2+ sparks) through ryanodine receptor 2 (RyR2), a sarcoplasmic reticulum-located channel that plays an essential role in cardiac excitation-contraction coupling, releasing the bulk Ca2+ required for contraction. We have recently identified that RyR2 is phosphorylated by casein kinase 2 (CK2), and that in vitro loss of this phosphorylation increases Ca2+ sparks. This project aimed to determine the role of CK2 phosphorylation of RyR2 in vivo. This was achieved using phospho-specific mutant mice, which expressed a variant of RyR2 unable to be phosphorylated by CK2 (S2692A/S2693A++).