The specific inhibition of the cardiac electrogenic sodium/bicarbonate cotransporter (NBCe1) leads to cardiac hypertrophy.

AIELLO EA; DI MATTÍA RA; ORLOWSKI A; CIANCIO MC

Buenos Aires

Congreso; XXII ISHR World Congress (International Society for Heart Research); 2016

The Na+/HCO3- cotransporter (NBC) regulates cardiac intracelular pH (pHi). There are two isoforms of NBC in the cardiomyocyte, the electrogenic NBCe1 (2 HCO3-: 1 Na+) and the electroneutral NBCn1 (1 HCO3-: 1 Na+). Both isoforms incorporate Na+ into the cell but the NBCe1 does it more efficiently because contributes with half of Na+ per HCO3-. The increase of Na+ enhances intracellular Ca2+ leading to cardiac hypertrophy (CH). We have previously demonstrated in CH models that while the activity of NBCe1 is reduced, that of the NBCn1 is increased. Due to the absence of specific pharmacological inhibitors we were unable to demonstrate if this phenomenon was cause or consequence of CH. We developed an interference RNA (shNBCe1) cloned in a lentiviral vector to study the effect of the specific inhibition of NBCe1 in CH. In western-blot assay we found a reduction of expression of NBCe1 in cells transduced with the shNBCe1 (cont: 100±5 %, n=4 vs shNBCe1: 15±2 %, n=4, P