L-type calcium channel abundance and function with cardiac hypertrophy and failure: a review

Calcium (Ca2+) influx through the L-type Ca2+ channels in cardiac myocytes is the initiating event in the excitation-contraction coupling process. In addition, augmentation of Ca2+ entry through the l-type Ca2+ channels is one means by which beta-adrenergic receptor stimulation increases the inotropic state of the myocyte. The purpose of this review is to summarize data with respect tol-type Ca2+ channel abundance and function in the setting of cardiac hypertrophy and congestive heart failure (CHF). Results from 54 studies on animal models of hypertrophy and heart failure and seven clinical studies of end-stage CHF have been included. In general, the development of severe hypertrophy and CHF in animal models is associated with abnormalities inl-type Ca2+ channel abundance and function. However, in these animal models, abnormalities inl-type Ca2+ channel function do not consistently manifest in milder forms of cardiac pathologies. Alterations inl-type Ca2+ channel function with end-stage human CHF remain equivocal. Nevertheless, in clinical studies as well as animal models,beta-adrenergic receptor mediated augmentation of L-type Ca2+ currents has been demonstrated to be reduced, in general, with hypertrophy and CHF. Future studies that examine the role of the L-type Ca2+ channel with respect to the excitation-contraction coupling process and myocyte contractility are warranted.