CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Acute exposure to high glucose causes arrhythmogenic effects in cardiomyocytes in a CaMKII dependent pathway.
Autor/es:
FEDERICO M; VILLA ABRILLE MC; J. PALOMEQUE; LÓPEZ S; ZAVALA M; MATTIAZZI A; NUOZZI G; SAID M
Lugar:
Beijing
Reunión:
Congreso; 2019 XXIII ISHR WORLD CONGRESS; 2019
Institución organizadora:
ISHR
Resumen:
The glycaemia is continuously fine-tuned according to our carbohydrate intake and consumption. However this regulation could be disrupted under certain metabolic conditions i.e. impaired glucose tolerance, metabolic syndrome and diabetes mellitus. Given that pre-diabetic and diabetic hearts present calcium (Ca2+) mishandling due in part by Ca2+-Calmodulin Kinase II (CaMKII), we hypothesized that an acute increase in glycaemia causes Ca2+ handling abnormalities capable to trigger arrhythmias in a CaMKII dependent pathway. The aim of the present work is to test this hypothesis.We used isolated mice cardiomyocytes loaded with Fura 2-AM to evaluate intracellular Ca2+ handling by epifluorescence, Langendorff perfused hearts to measure developed pressure (DP) and monophasic action potential (MAP) and hearts homogenates to perform [3H]Ryanodine binding assay to evaluate ryanodine receptor 2 (RyR2) activity.In cardiomyocytes, the change from normal glucose (NG) buffer (11 mM, 325.61mOsm) to high glucose (HG) buffer (25 mM, 339.26 mOsm) significantly increased Ca2+ transient (CaiT) amplitude (60.4±20.5%) and arrhythmogenic events (71.429%). A similar increment in osmolality induced by sucrose or choline chloride did not produced any effect either in CaiT or rhythmicity. The effects of HG were prevented by treatment with AIP (2.5µM), a specific CaMKII inhibitor. In Langendorff perfused heart, HG perfusion increased DP (30.0±3%) and produced ectopic beats with respect to NG perfusion. [3H]Ry binding assays showed a significantly increase in RyR2 sensitivity (1.05±0.27 vs 2.30±0.38µM) and maximal activity (Bmax: 48.09±2.35, vs 31.58±1.98) under HG vs. NG conditions.We conclude that acute administration of HG induces changes in Ca2+ handling and arrhythmic events that are dependent on CaMKII activation of RyR2. The increase in osmolality produced by HG would not be involved in the observed effects.