Cardiac Hypertrophy and Heart Failure

In cardiac and skeletal muscle, the sarcoplasmic reticulum (SR) plays a central role in the contraction relaxation cycle of the muscle by virtue of its ability to regulate the intracellular free Ca'+ concentration [Ca'+],. Ca'+ release from the SR increases [Ca'+] (10`mol/L), thus inducing contraction, whereas Ca2` uptake by the SR reduces [Ca'+] (=10-7 mol/L), producing muscle relaxation. In cardiac muscle, the beatto-beat rhythm (contraction-relaxation cycle) is tightly controlled by the regulated release and removal of Ca'+ by the SR. In view of this key role in excitationcontraction coupling, alterations in the SR function are expected to significantly affect cardiac performance. Over the past three decades, varying degrees of defects in the SR Ca'+ uptake function have been identified in different experimental models of heart disease, and the literature has been reviewed extensively.1 ~5More recent analyses using animal models and human failing heart samples suggest that alterations in SR function may be primarily due to alterations in the expression level of mRNAs encoding key SR Ca2' transport proteins. The purpose of this review is to highlight recent advances concerning the regulation of SR gene expression during cardiac hypertrophy and heart failure.