The Ca2+ ATPase of cardiac sarcoplasmic reticulum: Physiological role and relevance to diseases.

The Ca(2+) ATPase of sarcoplasmic reticulum has a prominent role in excitation/contraction coupling of cardiac muscle, as it induces relaxation by sequestering Ca(2+) from the cytoplasm. The stored Ca(2+) is in turn released to trigger contraction. We review here experiments demonstrating that in cardiac myocytes Ca(2+) signaling and contractile activation are strongly altered by pharmacological inhibition or transcriptional down-regulation of SERCA. On the other hand, kinetics, and intensity of Ca(2+) signaling are improved by SERCA overexpression following delivery of exogenous cDNA by adenovirus vectors. Experiments on adrenergic hypertrophy demonstrate SERCA down-regulation, consistent with its pathogenetic involvement in cardiac hypertrophy and failure, as also shown in other experimental models and clinical studies. Compensation by alternate Ca(2+) signaling proteins, including functional activation and increased expression of Na(+)/Ca(2+) exchanger and TRPC proteins has been observed. These compensatory mechanisms, including calcineurin activation, remain to be clarified and are a most important subject of current studies.