The histidine-rich Ca(2+) binding protein (HRC) is a high capacity Ca(2+) 
binding protein in the sarcoplasmic reticulum (SR). Because HRC appears to 
interact directly with triadin, HRC may play a role in the regulation of Ca(2+) 
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 Ca(2+) release from the SR were 
increased significantly in the HRC overexpressing cardiomyocytes. Consistently, 
the Ca(2+) 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)/Ca(2+) 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 Ca(2+) content into the SR.