title: Regulation of sarcoplasmic reticulum calcium release by luminal calcium in cardiac muscle.
abstract: The amount of Ca2+ released from the sarcoplasmic reticulum (SR) is a principal determinant of cardiac contractility. Normally, the SR Ca2+ stores are mobilized through the mechanism of Ca2+-induced Ca2+ release (CICR). In this process, Ca2+ enters the cell through plasmalemmal voltage-dependent Ca2+ channels to activate the Ca2+ release channels in the SR membrane. Consequently, the control of Ca2+ release by cytosolic Ca2+ has traditionally been the main focus of cardiac excitation-contraction (EC) coupling research. Evidence obtained recently suggests that SR Ca release is controlled not only by cytosolic Ca2+, but also by Ca2+ in the lumen of the SR. The presence of a luminal Ca2+ sensor regulating release of SR luminal Ca2+ potentially has profound implications for our understanding of EC coupling and intracellular Ca2+ cycling. Here we review evidence, obtained using in situ and in vitro approaches, in support of such a luminal Ca2+ sensor in cardiac muscle. We also discuss the role of control of Ca2+ release channels by luminal Ca2+ in termination and stabilization of CICR, as well as in shaping the response of cardiac myocytes to various inotropic influences and diseased states such as Ca2+ overload and heart failure.
authors.affiliation: Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6551, USA. sandor.gyorke@ttuhsc.edu
authors.forename: Sandor
authors.initials: S
authors.lastname: Györke
authors.forename: Inna
authors.initials: I
authors.lastname: Györke
authors.forename: Valeriy
authors.initials: V
authors.lastname: Lukyanenko
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Terentyev
authors.forename: Serge
authors.initials: S
authors.lastname: Viatchenko-Karpinski
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Wiesner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D002118:Calcium