Ca²⁺-calmodulin-dependent protein kinase II regulation of cardiac excitation-transcription coupling.

The multifunctional Ca-calmodulin-dependent protein kinase II (CaMKII) has emerged as a nodal point in cardiac muscle function and adaptation. This stems from CaMKII’s demonstrated role in phosphorylation and regulation of many key molecules known to be critical in excitation-contraction coupling and arrhythmias, and because it increases in expression and activation during hypertrophy and heart failure (HF) and CaMKII overexpression and suppression induce and suppress HF respectively. For many years, there were indications that intracellular Ca could activate altered gene expression, but only in the past ten years has it been recognized that CaMKII and a Ca-calmodulin-dependent phosphatase calcineurin are major Ca-dependent mediators of transcriptional regulation. Moreover, these pathways contribute to changes in gene expression of proteins involved in the HF phenotype, including some of the ion channels and Ca transporters that are acutely involved in systolic dysfunction and arrhythmias.