Calcium Channels in Cardiac Hypertrophy and Heart Failure

With the development of cardiac hypertrophy and heart failure, there are profound alterations in the ability of the cardiac cell to contract and relax. Despite several decades of intensive investigation, the precise cellular mechanisms responsible for this contractile dysfunction remain unknown. Recent advances in confocal microscopy and fluorescent calcium (Ca⊃2⊃+) indicators have allowed investigators to image the focal release of Ca⊃2⊃+ from the sarcoplasmic reticulum for the first time. The use of these techniques offers the unique opportunity to study the elemental events of excitation–contraction coupling in diseased myocardium. In this review, we focus on the role of calcium channels (L-type and T-type) and the TTX-sensitive Ca⊃2⊃+-permeable sodium (Na⊃+) channel in normal and abnormal cardiac function. Additionally, the role of the sodium–calcium exchanger and the voltage-activated process in cardiac excitation–contraction coupling is discussed. The application of newer microscopic techniques to study animal models that mimic human disease longitudinally will provide the means to identify precisely the abnormalities in calcium handling that occur with the development of cardiac hypertrophy and heart failure. This revised version was published online in July 2006 with corrections to the Cover Date.