title: Alterations in calcium handling in cardiac hypertrophy and heart failure.
abstract: There is conflicting data concerning the effects of cardiac hypertrophy and failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+ transients, and the characteristics of Ca2+ sparks. These discrepancies are probably due to multiple factors. First, the effects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by which cardiac hypertrophy and heart failure are generated (genetic alteration, pressure overload, volume overload, high rate pacing, etc.) influence the results obtained. Second, with many animal models and diseased human hearts, the disease process is not uniformly distributed throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and SR function clearly depend on the extent of disease expression. Myocardial contractility increases with cardiac hypertrophy whereas it decreases with heart failure. Thus, it is difficult to compare results from different models of hypertrophy and heart failure at different stages of disease. More consistent data is likely to be obtained from longitudinal studies using a single animal model of disease. The challenge before us is to develop animal models that mimic human disease, which can be studied longitudinally during the progression of the disease process. This approach coupled with continued improvement in Ca2+ imaging and a greater understanding of normal E-C coupling, will enable us to identify precisely the abnormalities in E-C coupling that occur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA. bbalke@heart.ab.umd.edu
authors.forename: C W
authors.initials: CW
authors.lastname: Balke
authors.forename: S R
authors.initials: SR
authors.lastname: Shorofsky
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000252:Calcium-Transporting ATPases; D002118:Calcium