of SR Ca2 release by the triadin-to-calsequestrin ratio in ventricular

Calsequestrin (CSQ) is a Ca2 storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca2 signaling complex in the cardiac junc-tional sarcoplasmic reticulum (SR). Heart-specific overexpression of CSQ in transgenic mice (TGCSQ) was associated with heart failure, attenuation of SR Ca2 release, and downregulation of associated junc-tional SR proteins, e.g., TRN. Hence, we tested whether co-overexpres-sion of CSQ and TRN in mouse hearts (TGCxT) could be beneficial for impaired intracellular Ca2 signaling and contractile function. Indeed, the depressed intracellular Ca2 concentration ([Ca]i) peak amplitude in TGCSQ was normalized by co-overexpression in TGCxT myocytes. This effect was associated with changes in the expression of cardiac Ca2 regulatory proteins. For example, the protein level of the L-type Ca2 channel Cav1.2 was higher in TGCxT compared with TGCSQ. Sarco(en-do)plasmic reticulum Ca2-ATPase 2a (SERCA2a) expression was re