Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 7, Issue -, Pages E263-E275Publisher
IMR PRESS
DOI: 10.2741/benitah
Keywords
heart failure; excitation-contraction coupling; Ca2+ signaling; [Ca2+](i) transient; Ca2+ sparks; L-type Ca2+ current; ryanodine receptors; review
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Heart failure (HF) is a progressive syndrome that appears as the final phase of most cardiac diseases and is manifested as a decreased contractile function. Contraction in cardiomyocytes arises by the Ca2+ induced Ca2+ release mechanism, where Ca2+ entry (I-Ca through Ca2+ channels (DHPRs) activates Ca2+ release channels (RyRs) in the junctional sarcoplasmic reticulum (SR). This is the base of cardiac excitation-contraction (EC) coupling. To elucidate the mechanisms underlying depressed function of the failing heart, analysis of EC coupling main elements have been undertaken. I-Ca density is usually maintained in HF. However, failing myocytes show a reduced SR Ca2+ release. Then, if the trigger of SR Ca2+ release is maintained, why is SR Ca2+ release depressed in HF? Analyses of the DHPR-RyR coupling efficiency have revealed a decrease in the I-Ca efficacy to trigger Ca2+ release in failing myocytes. In terminal heart failure without hypertrophy, a decrease in SR Ca2+ load can account for the decreased SR Ca2+ release. Fewer Ca2+ sparks ( elementary units of SR Ca2+ release) are triggered by an equivalent I-Ca in hypertrophied failing myocytes, suggesting a functional or spatial reorganization of the space T-tubule junctionnal SR. This theory is supported by new data showing that the T-tubule density is reduced in failing cells.
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