title: [Excitation-Contraction coupling and intracellular calcium cycling in failing hearts].
abstract: Alterations in Excitation-Contraction coupling have recently been shown to play a crucial role in the pathogenesis of heart failure (HF). In failing hearts, abnormalities of neurohormonal mechanisms, which were included chronic activation of the sympathetic nervous system or of the renin-angiotensin system result in structural and functional changes in the calcium (Ca(2 +) ) regulatory proteins. These changes include the decreased sarcoplasmic reticulum (SR) load, which could be caused by reduced SR Ca(2 +) -ATPase (SERCA2A) function and increased SR Ca(2 +) leak via cardiac ryanodine receptor (RyR2) , a functional defect in L-type Ca(2 +) channel and activation of the reversal mode of Na (+) /Ca(2 +) exchanger. The abnormal regulation of intracellular Ca(2 +) affects troponin C binding and actin-myosin cross bridging and modulates post signaling pathway, which in turn contributes to the contractile dysfunction of hearts and hence to the progression of HF. Moreover, diastolic Ca(2 +) leak may develop delayed after depolarization and triggered activity as a substrate for lethal arrhythmia and sudden cardiac death. In this review, we focus on the underlying mechanism of defective Ca(2 +) regulation in HF and on the possibility of proceeding to clinical application as a new treatment for HF by targeting Ca(2 +) regulatory proteins.
authors.affiliation: Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okuda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D056966:Excitation Contraction Coupling / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium