Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calmodulin (CaM) is a ubiquitously expressed Ca2+ binding protein best known for its ability to activate CaM-dependent kinases in a variety of cells. It was initially identified in its role as an activator of cAMP PDE. In fact, calmodulin was first known as the calcium-dependent regulator protein of PDE. Calmodulin is involved, directly and indirectly, in modulation of several ion channels, including Na+, K+, L-type Ca2+, and RYR2 channels. The main binding partner of calmodulin in cardiac cells is RyR2, which regulates Ca2+ release from the sarcoplasmic reticulum. Acting as an intracellular Ca2+ sensor, Ca2+-saturated calmodulin binds RYR2 to inhibit Ca2+ release by stabilizing the RyR2 channel closed state.
