title: Store-dependent deactivation: cooling the chain-reaction of myocardial calcium signaling.
abstract: In heart cells, Ca(2+) released from the internal storage unit, the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR2) channels is the predominant determinant of cardiac contractility. Evidence obtained in recent years suggests that SR Ca(2+) release is tightly regulated not only by cytosolic Ca(2+) but also by intra-store Ca(2+) concentration. Specifically, Ca(2+)-induced Ca(2+) release (CICR) that relies on auto-catalytic action of Ca(2+) at the cytosolic side of RyR2s is precisely balanced and counteracted by RyR2 deactivation dependent on a reciprocal decrease of Ca(2+) at the luminal side of RyR2s. Dysregulation of this inherently unstable Ca(2+) signaling is considered to be an underlying cause of triggered arrhythmias, and is associated with genetic and acquired forms of sudden cardiac death. In this article, we present an overview of recent advances in our understanding of the regulatory role luminal Ca(2+) plays in Ca(2+) handling, with a particular emphasis on the role of Ca(2+)release refractoriness in aberrant Ca(2+) release.
authors.affiliation: The Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA.
authors.forename: Przemysław B
authors.initials: PB
authors.lastname: Radwański
authors.forename: Andriy E
authors.initials: AE
authors.lastname: Belevych
authors.forename: Lucia
authors.initials: L
authors.lastname: Brunello
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: Sándor
authors.initials: S
authors.lastname: Györke
mesh_terms: D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D016757:Death, Sudden, Cardiac / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium