CONICET | Buscador de Institutos y Recursos Humanos

CaMKII and osmolarity are involved in the arrhythmogenic effect of mouse cardiomyocytes exposed to extracellular high glucoseFederico M, Nuozzi G, Lopez S, Zabala M, Villa Abrille MC, Cely Ortiz A,Mattiazzi A, Palomeque J.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, we hypothesized that an acute increase in glycaemia causes Ca2+ handling abnormalities capable to trigger arrhythmias. The aim of the present work is to test our hypothesis and elucidate the intracellular pathways. We used isolated mice cardiomyocytes loaded with Fura-2AM to evaluate intracellular Ca2+ handling by epifluorescence. 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 accelerated CaiT relaxation, although without reaching significant levels. These results were completely normalized with AIP, a highly specific CaMKII inhibitor. On the other hand, HG produced arrhytmogenic events that were significantly reverted by 48.2% with AIP. The same increase in osmolarity by manitol (13.9 mM, 339.26 mOsm), did not modify CaiT amplitude or Ca2+ dynamics and induced arrhytmogenic events that also decreased with AIP, although in a significantly lower percentage (24.5%) than HG. We conclude that acute administration of HG induces changes in Ca2+ handling and arrhythmic events that are dependent on CaMKII. We could not discard that the results observed were influenced, in part, by the osmotic effect of HG perfusion. We speculate that HG and hiperosmolarity per se induced arrhythmic effects by different intracellular pathways.