Sarco/endoplasmic reticulum Ca2+ (SERCA)-pumps: link to heart beats and calcium waves

Mobilization of endoplasmic reticulum Ca2+ is pivotal to the ability of a c ell to send or respond to stimuli. Ca2+-Mg2+-ATPases, termed SERCA pumps, s equester Ca2+ into the sarco/endoplasmic reticulum. There are several SERCA protein isoforms encoded by three genes. This paper summarizes the structu re, function, tissue and subcellular distribution, and regulation of variou s SERCA isoforms. Then it attempts to link divergence in the signal transdu ction processes of cells to the types and levels of SERCA proteins they exp ress and to how the cells regulate their SERCA pump activity. The paper exa mines possible linkages between SERCA pumps and receptor-activated Ca2+ ent ry, SERCA isoform localization and Ca2+-waves, and the role of SERCA pumps in nuclear Ca2+ in cell proliferation and apoptosis. Then it uses available information on cardiac function and chronic stimulation of the fast-twitch muscle to answer a series of basic questions on the regulation of SERCA ac tivity and expression and their linkage to signal transduction. Finally, it discusses the possibility that neurons exhibit complex Ca2+-waves whose in teractions have the potential to explain the operational basis of neural ne tworks. A series of unanswered questions emerge based on this synthesis, in cluding the unsettling issue of whether all the isoforms are needed to achi eve the divergence in signal transduction or if there is a degree of redund ancy in the system.