title: Altered communication between L-type calcium channels and ryanodine receptors in heart failure.
abstract: 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 (ICa) 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. ICa 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 ICa 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 ICa in hypertrophied failing myocytes, suggesting a functional or spatial reorganization of the space T-tubule junctional SR. This theory is supported by new data showing that the T-tubule density is reduced in failing cells.
authors: INSERM U-390, Montpellier, France.
authors: Jean-Pierre
authors: JP
authors: Bénitah
authors: Benoît Gilles
authors: BG
authors: Kerfant
authors: Guy
authors: G
authors: Vassort
authors: Sylvain
authors: S
authors: Richard
authors: Ana María
authors: AM
authors: Gómez
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium