CARDIOMYOCYTE GROWTH-REGULATION BY CA2+-CALMODULIN

Elevation of intracellular free Ca2+ concentrations is a common early cellular action of a variety of agents that induce cardiac myocyte hypertrophy. This observation, plus the large body of evidence that implicates Ca2+-calmodulin (CaM) in cell-cycle control in other cells, prompted us to evaluate the role of the CaM signal-transducing pathway in cardiomyocyte growth regulation. Toward that end, several lines of transgenic mice were generated to express elevated levels of CaM in cardiac myocytes during development. Constitutive overexpression of CaM in the hearts of transgenic mice induced both hyperplastic and hypertrophic growth of cardiac myocytes; some characteristics and potential mechanisms of this growth response are the subjects of the present review.