Calmodulin and the plasma membrane calcium pump.
The data summarized and presented in this paper are consistent with the interpretation that CaM participates in the regulation of the plasma membrane calcium pump. Certain drugs, such as phenothiazines can antagonize CaM. Ca2+ loading of RBCs promotes CaM binding to RBC membranes and results in decreased responsiveness of the [Ca2+ + Mg2+)-ATPase to CaM. The latter effect may be mediated by a Ca2+ activated transglutaminase. Activation of (Ca2+ + Mg2+)-ATPase by CaM in vitro was shown not to be instantaneous, probably because of slow binding. CaM binding to isolated RBC membranes exhibits a Ca2+ dependence that is similar to that for activation of the (Ca2+ + Mg2+)-ATPase, and CaM binding does not decrease at high [Ca2+]s. Calculations based on assumed values for RBC [Ca2+], [CaM], and binding affinities of Ca2+ for CaM and CaM(Ca2+)n for the Ca2+ pump ATPase resulted in the tentative conclusion that most pump sites are occupied by CaM in the RBC in vivo. This conclusion, and the relatively slow time course of the CaM effect on (Ca2+ + Mg2+)-ATPase prompt us to suggest that, for all practical purposes, CaM is a subunit of the Ca2+ pump ATPase in vivo.
D000251:Adenosine Triphosphatases / Q000097:blood; D001693:Biological Transport, Active / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000097:blood*; D002147:Calmodulin / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000097:blood; D010042:Ouabain / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D008565:Membrane Proteins; D000001:Calcimycin; D010042:Ouabain; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium; D002746:Chlorpromazine