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

• Published in: FEBS letters 1999-01, Vol.443 (3), p.308-312
• Main Authors: Nediani, Chiara, Fiorillo, Claudia, Rigacci, Stefania, Magherini, Francesca, Francalanci, Michela, Liguri, Gianfranco, Pacini, Alessandra, Nassi, Paolo
• Format: Article
• Language: English
• Subjects: Acid Anhydride Hydrolases - genetics; Acid Anhydride Hydrolases - metabolism; Acid Anhydride Hydrolases - pharmacology; Acylphosphatase; Adenosine Triphosphate - metabolism; Animals; Calcium - metabolism; Calcium-Binding Proteins - physiology; Calcium-Transporting ATPases - drug effects; Calcium-Transporting ATPases - metabolism; Cattle; Cyclic AMP-Dependent Protein Kinases - metabolism; Dose-Response Relationship, Drug; EP, phosphoenzyme; Heart - drug effects; Heart sarcoplasmic reticulum Ca 2+ pump; Heart sarcoplasmic reticulum Ca2+ pump; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Mutation; Myocardium - metabolism; Organelles - drug effects; Organelles - metabolism; Phosphates - metabolism; Phospholamban; Phosphorylation - drug effects; PKA, cAMP-dependent protein kinase; PLN, phospholamban; Precipitin Tests; Rabbits; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - metabolism; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum; SRV, SR vesicle
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01717-7

In cardiac and skeletal muscle Ca 2+ translocation from cytoplasm into sarcoplasmic reticulum (SR) is accomplished by different Ca 2+-ATPases whose functioning involves the formation and decomposition of an acylphosphorylated phosphoenzyme intermediate (EP). In this study we found that acylphosphatase, an enzyme well represented in muscular tissues and which actively hydrolyzes EP, had different effects on heart (SERCA2a) and fast twitch skeletal muscle SR Ca 2+-ATPase (SERCA1). With physiological acylphosphatase concentrations SERCA2a exhibited a parallel increase in the rates of both ATP hydrolysis and Ca 2+ transport; in contrast, SERCA1 appeared to be uncoupled since the stimulation of ATP hydrolysis matched an inhibition of Ca 2+ pump. These different effects probably depend on phospholamban, which is associated with SERCA2a but not SERCA1. Consistent with this view, the present study suggests 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.