title: Stanniocalcin-1 is a naturally occurring L-channel inhibitor in cardiomyocytes: relevance to human heart failure.
abstract: Cardiomyocytes of the failing heart undergo profound phenotypic and structural changes that are accompanied by variations in the genetic program and profile of calcium homeostatic proteins. The underlying mechanisms for these changes remain unclear. Because the mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is expressed in the heart, we reasoned that STC1 might play a role in the adaptive-maladaptive processes that lead to the heart failure phenotype. We examined the expression and localization of STC1 in cardiac tissue of patients with advanced heart failure before and after mechanical unloading using a left ventricular assist device (LVAD), and we compared the results with those of normal heart tissue. STC1 protein is markedly upregulated in cardiomyocytes and arterial walls of failing hearts pre-LVAD and is strikingly reduced after LVAD treatment. STC1 is diffusely expressed in cardiomyocytes, although nuclear predominance is apparent. Addition of recombinant STC1 to the medium of cultured rat cardiomyocytes slows their endogenous beating rate and diminishes the rise in intracellular calcium with each contraction. Furthermore, using whole cell patch-clamp studies in cultured rat cardiomyocytes, we find that addition of STC1 to the bath causes reversible inhibition of transmembrane calcium currents through L-channels. Our data suggest differential regulation of myocardial STC1 protein expression in heart failure. In addition, STC1 may regulate calcium currents in cardiomyocytes and may contribute to the alterations in calcium homeostasis of the failing heart.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Sheikh@bcm.tmc.edu
authors.forename: David
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.forename: Roger
authors.initials: R
authors.lastname: Bick
authors.forename: Gang-Yi
authors.initials: GY
authors.lastname: Wu
authors.forename: Birgitte Mønster
authors.initials: BM
authors.lastname: Christensen
authors.forename: Peter
authors.initials: P
authors.lastname: Razeghi
authors.forename: Brian
authors.initials: B
authors.lastname: Poindexter
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.forename: Ann
authors.initials: A
authors.lastname: Wamsley
authors.forename: Ranjit
authors.initials: R
authors.lastname: Padda
authors.forename: Mark
authors.initials: M
authors.lastname: Entman
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Keith
authors.initials: K
authors.lastname: Youker
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006728:Hormones / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D006023:Glycoproteins; D006728:Hormones; D009553:Nimodipine; C051795:teleocalcin; D002118:Calcium