USE OF ADENO-ASSOCIATED VIRAL VECTORS FOR SILENCING AND OVEREXPRESSION OF THE CARDIAC ELECTROGENIC BICARBONATE SODIUM COTRANSPORTER

DI MATTÍA RA

Mar del Plata

Simposio; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. Two alkalinizing mechanisms coexist in cardiac myocytes: sodium/bicarbonate cotransporter (electroneutral isoform NBCn1 and electrogenic isoform NBCe1) and sodium/proton exchanger (NHE1). NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). In addition to regulating the pH, the NBC is a source of sodium influx. It has been postulated that NBC could play a role in the development of hypertrophy. The aim of this research was to study the contribution of NBCe1 in heart electrophysiology and in the development of heart hypertrophy in an in vivo model. We used recombinant cardiotropic adenoassociated virus (AAV9) to achieve NBCe1 overexpression (AAV9-NBCe1) and NBCe1 silencing (AAV9-shNBCe1) in mice and rats, respectively. Patch clamp and electrocardiogram were performed. In both cases, we observed APD and electrocardiogram QT interval corrected by cardiac rate significant changes, emphasizing for the first timE NBCe1 relevance for the electrical activity of the heart. Furthermore, the downregulation of NBCe1 caused significant hypertrophic heart growth and increased the frequency of Ca2+ waves without any significant changes in Ca2+ transients. An increased compensatory expression of NBCn1 and NHE1 was also found. We conclude that the reduction of NBCe1 is sufficient to induce cardiac hypertrophy without changes in blood pressure.