title: STIM1 participates in the contractile rhythmicity of HL-1 cells by moderating T-type Ca(2+) channel activity.
abstract: STIM1 plays a crucial role in Ca(2+) homeostasis, particularly in replenishing the intracellular Ca(2+) store following its depletion. In cardiomyocytes, the Ca(2+) content of the sarcoplasmic reticulum must be tightly controlled to sustain contractile activity. The presence of STIM1 in cardiomyocytes suggests that it may play a role in regulating the contraction of cardiomyocytes. The aim of the present study was to determine how STIM1 participates in the regulation of cardiac contractility. Atomic force microscopy revealed that knocking down STIM1 disrupts the contractility of cardiomyocyte-derived HL-1 cells. Ca(2+) imaging also revealed that knocking down STIM1 causes irregular spontaneous Ca(2+) oscillations in HL-1 cells. Action potential recordings further showed that knocking down STIM1 induces early and delayed afterdepolarizations. Knocking down STIM1 increased the peak amplitude and current density of T-type voltage-dependent Ca(2+) channels (T-VDCC) and shifted the activation curve toward more negative membrane potentials in HL-1 cells. Biotinylation assays revealed that knocking down STIM1 increased T-VDCC surface expression and co-immunoprecipitation assays suggested that STIM1 directly regulates T-VDCC activity. Thus, STIM1 is a negative regulator of T-VDCC activity and maintains a constant cardiac rhythm by preventing a Ca(2+) overload that elicits arrhythmogenic events.
authors: Department of Pharmacology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Nathalie
authors: N
authors: Nguyen
authors: Michael
authors: M
authors: Biet
authors: Elie
authors: E
authors: Simard
authors: Eric
authors: E
authors: Béliveau
authors: Nancy
authors: N
authors: Francoeur
authors: Gaétan
authors: G
authors: Guillemette
authors: Robert
authors: R
authors: Dumaine
authors: Michel
authors: M
authors: Grandbois
authors: Guylain
authors: G
authors: Boulay
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009119:Muscle Contraction; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1; D013610:Tachycardia
chemical_list: D015220:Calcium Channels; D020747:Calcium Channels, T-Type; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium