Cardiac calmodulin and its role in the regulation of metabolism and contraction

Abstract

Calmodulin, the ubiquitous and multifunctional Ca 2+-dependent regulatory protein, is capable of activating a number of enzymes through the formation of active ternary complexes Ca 2+-calmodulin-enzyme, upon increase of the cytosolic Ca 2+ level from pCa 8 to pCa 5. In cardiac muscle, calmodulin is involved in the Ca 2+-dependent activation of cyclic nucleotide phosphodiesterase and, perhaps, inhibition of adenylate cyclase. Cardiac and vascular myosin light chain kinases are also Ca 2+-calmodulin-dependent. Whereas light chain phosphorylation is required for vascular smooth muscle contraction, the effect of cardiac myosin phosphorylation is as yet unknown. Calmodulin is involved in the control of the phosphorylation of the sarcoplasmic reticulum Ca 2+ pump activator, phospholamban, thereby modulating the rate of Ca 2+ uptake. Calmodulin is likely to be a subunit of cardiac glycogen phosphorylase b kinase, that triggers glycogen breakdown and presumably inhibits glycogen synthesis. Finally calmodulin binds to other calmodulin-binding proteins of hitherto unknown function.