A novel interaction mechanism accounting for different acylphosphatase effects on cardiac and fast twitch skeletal muscle sarcoplasmic reticulum calcium pumps

In cardiac and skeletal muscle Ca2+ translocation front cytoplasm into sarc oplasmic reticulum (SR) is accomplished by different Ca2+-ATPases whose fun ctioning involves the formation and decomposition of an acylphosphorylated phosphoenzyme intermediate (EP), In this study we found that acylphosphatas e, an enzyme well represented in muscular tissues and which actively hydrol yzes EP, had different effects on heart (SERCA2a) and fast twitch skeletal muscle SR Ca2+-ATPase (SERCA1), With physiological acylphosphatase concentr ations SERCA2a exhibited a parallel increase in the rates of both ATP hydro lysis and Ca2+ transport; in contrast, SERCA1 appeared to be uncoupled sinc e the stimulation of ATP hydrolysis matched an inhibition of Ca2+ pump. The se different effects probably depend on phospholamban, which is associated with SERCA2a but not SERCA1, Consistent with this view, the present study s uggests that acylphosphatase-induced stimulation of SERCA2a, in addition to an enhanced EP hydrolysis, may be due to a displacement of phospholamban, thus to a removal of its inhibitory effect. (C) 1999 Federation of European Biochemical Societies.