ABSTRACT

The regulation of cytoplasmic Ca2+ during rest and activity requires a delicate balance between Ca2+ pumps, Ca2+ channels, Na+/Ca2+ exchanger, and Ca2+-binding proteins that influence the distribution of Ca2+ in muscle cells. This balance implies that the various components are present in matched concentrations, requiring coordinate regulation of their rate of synthesis and degradation. The regulation is likely to be complex combining myogenic and neural mechanisms, controlled by chemical and mechanical signals acting at various levels of the gene expression hierarchy. The details of the mechanisms are only beginning to emerge, but the constellation of phenomena clearly point at Ca2+ as one of the principal regulators. There is a close correlation between the contractile activity of the muscle and the level of expression of various muscle proteins both during development and in mature animals. The sharp increase in the content of Ca2+ ATPase and other Ca2+ regulatory proteins during embryonic development coincides with innervation and the onset of contractile activity (Martonosi, 1982a). The relative abundance of sarcoplasmic reticulum in various muscles is roughly proportional to their rate of contraction and relaxation. Fast-acting, “white” skeletal muscles contain greater amount of sarcoplasmic reticulum and possess higher Ca2+-ATPase content than the slower “red” skeletal, cardiac or smooth muscles (Fawcett and Revel, 1961; Revel, 1962; Rosenbluth, 1969; Lytton and MacLennan, 1991; Gibbons and Zygmunt, 1991; Dux, 1993; Hollingworth et al., 1996; Rome et al., 1996; Raeymaekers and Wuytack, 1996; Pette and Staron, 1997; Karaki et al., 1997). At the very slow end of the spectrum specialized sarcoplasmic reticulum is virtually absent in the slow, small muscle fibers of Doliolum (Bone et al., 1997), where its role is taken over by the Na: Ca2+ exchanger.