CONICET | Buscador de Institutos y Recursos Humanos

Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of the myocardium which commonly leads to heart failure. Myocardial intracellular pH (pHi) in the heart is regulated by acid/base transporters (ABT) such as the NHE1 Na+/H+ exchanger, the NBC Na+/HCO3- cotransporter, and the AE Cl-/HCO3- exchanger, among others. pHi alterations lead to changes in heart function and changes in the activity/expression of NHE1, NBC, and AE have been associated with cardiac disorders. Conversely, carbonic anhydrases (CAs) enzymes are widely distributed in all organs and tissues, catalyzing the reversible conversion of CO2/HCO3-. Functional/physical interaction between CA and the AE, NBC, and NHE ABT occurs in cardiac muscle cells, maximizing ion fluxes, creating a membrane transport metabolon (MTM). Herein, we study the role of the MTM in cardiac dysfunction linked to obesity and DC. We characterized the expression and function of CA, and NHE1 and NBC ABT, using an obese mice model (C57BL6 ob-/- mice). So far our results showed DC features in the heart of ob-/- female mice starting as soon as 8 weeks old, characterized by an increased septum thickness and posterior wall thickness, and increased left ventricular diameter. Furthermore, ob-/- mice had increased left ventricular mass and left ventricular mass index, indicating cardiac hypertrophy. To study the role of NHE1 in the ob-/- and wild type (ob+/+) mice, isolated cardiomyocytes were loaded with the BCECF-AM fluorescent dye and the NHE1-dependent pHi recovery measured in myocytes subjected to NH4Cl-induce acid loading, monitored by epifluorescence. Preliminary results showed increased NHE1 activity in the hypertrophic myocardium of ob-/- compared to ob+/+ mice, 0.30 ± 0.02 vs. 0.20 ± 0.02 pH units.min-1.100, respectively (n= 5, p