Key result
SDF-1α signaling through CXCR4 significantly increased calcium transients in an IP3-gated fashion and induced a positive chronotropic and inotropic effect in rat neonatal cardiomyocytes.
SDF-1α enhances calcium transients and beating frequency in rat neonatal cardiomyocytes via CXCR4 and IP3 receptors, providing a mechanism for its early inotropic effects.
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Hypothesis-generating for SDF-1α inotropy in neonatal cardiomyocytes; leaves open translation to adult human myocardium.
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.
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Hadad et al. (2013) studied Myocardial function (n=8). Stroma Cell-Derived Factor-1α (SDF-1α) vs. Buffer / Placebo was evaluated on Cytoplasmic calcium release (maximal fractional change in fluorescence ΔF/F0) (p=<0.01). SDF-1α signaling through CXCR4 significantly increased calcium transients in an IP3-gated fashion and induced a positive chronotropic and inotropic effect in rat neonatal cardiomyocytes.
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