SERCA pump level is a critical determinant of Ca2+ homeostasis and cardiaccontractility

The control of intracellular calcium is central to regulation of cardiac co ntractility, A defect in SR Ca2+ transport and SR Ca2+ ATPase pump activity and expression level has been implicated as a major player in cardiac dysf unction, However, a precise cause-effect relationship between alterations i n SERCA pump level and cardiac contractility could not be established from these studies. Progress in transgenic mouse technology and adenoviral gene transfer has provided new tools to investigate the role of SERCA pump level in the heart. This review focuses on how alterations in SERCA level affect Ca2+ homeostasis and cardiac contractility. It discusses the consequences of altered SERCA pump levels for the expression and activity of other Ca2handling proteins. Furthermore, the use of SERCA pump as a therapeutic targ et for gene therapy of heart failure is evaluated. (C) 2001 Academic Press.