Increased Ca²⁺ storage capacity in the sarcoplasmic reticulum by overexpression of HRC (histidine-rich Ca²⁺ binding protein)

The histidine-rich Ca²⁺ binding protein (HRC) is a high capacity Ca²⁺ binding protein in the sarcoplasmic reticulum (SR). Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca²⁺ release during excitation-contraction coupling. In this study, we examined the physiological effects of HRC overexpression in rat neonatal cardiomyocytes. Both caffeine-induced and depolarization-induced Ca²⁺ release from the SR were increased significantly in the HRC overexpressing cardiomyocytes. Consistently, the Ca²⁺ content, normally depleted from the SR in the presence of cyclopiazonic acid (CPA), remained elevated in these cells. In contrast, the density and the ryanodine-binding kinetics of the ryanodine receptor (RyR)/Ca²⁺ release channel were slightly reduced or not significantly altered in the HRC overexpressing cardiomyocytes. We suggest that HRC is involved in the regulation of releasable Ca²⁺ content into the SR.