title: Defective Ca2+ cycling as a key pathogenic mechanism of heart failure.
abstract: Structural and functional alterations in the Ca(2+) regulatory proteins present in the sarcoplasmic reticulum (SR) have recently been shown to play a crucial role in the pathogenesis of heart failure (HF), and lethal arrhythmia as well. Chronic activation of the sympathetic nervous system induces abnormalities in both the function and structure of these proteins. For instance, the diastolic Ca(2+) leak through the SR Ca(2+) release channel (ryanodine receptor) reduces the SR Ca(2+) content, inducing contractile dysfunction. Moreover, the Ca(2+) leak provides a substrate for delayed after depolarization that leads to lethal arrhythmia. There is a considerable body of evidence regarding the role of Ca(2+) cycling abnormality in HF.
authors.affiliation: Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan. yanoma@yamaguchi-u.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000401:mortality; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium