Characterization of calmodulin effects on calcium transport in cardiac microsomes enriched in sarcoplasmic reticulum.
Calmodulin prepared from red cell hemolysates was found to significantly increase Ca2+ uptake into cardiac microsomal preparations enriched in sarcoplasic reticulum in a dose-dependent manner. The stimulation of calcium uptake by calmodulin was additive to that stimulation produced by maximal stimulatory concentrations of adenosine cyclic 3',5'-phosphate (cAMP) dependent protein kinase and cAMP, indicating separate mechanisms of action and potentially different modulatory roles for these two systems in the control of calcium transport. K+ significantly decreased calmodulin stimulation of calcium uptake, while in the absence of calmodulin, K+ increased Ca2+ uptake. In the absence of K+, calmodulin increased Ca2+ uptake to levels observed at maximal K+ concentrations without calmodulin present. Na+ produced effects similar to those of K+ in this preparation both in the presence and absence of calmodulin. The effect of calmodulin on the intermediate steps of the (Mg2+,Ca2+)ATPase in cardiac sarcoplasmic reticulum was also investigated. Calmodulin was found to reduce the steady-state level of the Ca2+-dependent phosphoprotein (ECaP) and increase the (Mg2+,Ca2+)ATPase activity of this preparation. Dephosphorylation of ECaP in the presence of Tris-ATP (0.5 mM) was significantly stimulated by calmodulin. These studies indicate that calmodulin stimulates Ca2+ transport in cardiac sarcoplasmic reticulum by increasing the turnover rate of the transport process.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000097:blood / Q000494:pharmacology*; D002414:Cations, Monovalent; D000242:Cyclic AMP / Q000494:pharmacology; D004285:Dogs; D004912:Erythrocytes / Q000032:analysis; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002414:Cations, Monovalent; D012964:Sodium; D000242:Cyclic AMP; D011494:Protein Kinases; D002118:Calcium