title: Stroma cell-derived factor-1α signaling enhances calcium transients and beating frequency in rat neonatal cardiomyocytes.
abstract: Stroma cell-derived factor-1α (SDF-1α) is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R) blocker, but not with a ryanodine receptor (RyR) antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.
authors: Department of Physiopathology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. ielham.hadad@ulb.ac.be
authors: Ielham
authors: I
authors: Hadad
authors: Alex
authors: A
authors: Veithen
authors: Jean-Yves
authors: JY
authors: Springael
authors: Panagiota A
authors: PA
authors: Sotiropoulou
authors: Agnès
authors: A
authors: Mendes Da Costa
authors: Françoise
authors: F
authors: Miot
authors: Robert
authors: R
authors: Naeije
authors: Xavier
authors: X
authors: De Deken
authors: Kathleen Mc
authors: KM
authors: Entee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism* / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019718:Receptors, CXCR4; D019837:Ryanodine Receptor Calcium Release Channel; D019210:Troponin I; D005576:Colforsin; D053148:Caspase 3