Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca2homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca2influx into the myocyte, Ca2release from the sarcoplasmic reticulum (SR), SR Ca2uptake and Naand Kchannel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Regulates Ca2influx to myocytes by binding and phosphorylating the L-type Ca2channel subunit beta-2 CACNB2. In addition to Ca2channels, can target and regulate the cardiac sarcolemmal Nachannel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca2uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis.
