Ion transport mechanism of the sarcoplasmic reticulum Ca-ATPase and its regulation by drugs investigated by a concentration jump method

The physiological task of the Ca-ATPase of the sarcoplasmic reticulum (SR) is to promote muscle relaxation by pumping Ca2+ ions from the cytoplasm into the SR lumen at the expense of the chemical energy provided by the hydrolysis of ATP. SR native vesicles and microsomes containing recombinant Ca-ATPase (wild type and mutants) were adsorbed on an octadecanethiol/phosphatidylcholine mixed bilayer anchored to a gold electrode, and the Ca-ATPase was activated by Ca2+ and ATP concentration jumps through a rapid solution exchange. Current transients were measured following Ca2+ concentration jumps in the absence of ATP, and following ATP concentration jumps in the presence of Ca2+ both on native and recombinant SR Ca-ATPase. These charge movements are attributed to the binding of calcium ions to the enzyme in the ground state and to their release from the enzyme phosphorylated by ATP. The effect of different drugs on the ion transport mechanism of the SR Ca-ATPase has been investigated (1). More recently, our attention has been focused on the interaction between the calcium pump and Sr2+-based compounds of pharmacological interest, e.g. strontium ranelate, which are used for the prevention and treatment for osteoporosis and related bone diseases (2). The authors wish to thank Prof. Giuseppe Inesi for providing them with native and recombinant SR Ca-ATPase. Ente Cassa di Risparmio di Firenze is gratefully acknowledged for financial support (PROMELAB project). 1. Bartolommei, G., F. Tadini-Buoninsegni, S. Hua, M.R. Moncelli, G. Inesi, and R. Guidelli. 2006. J. Biol. Chem. 281:9547-9551. 2. Fuleihan, G.el-H. 2004. N. Engl. J. Med. 350:504-506.