Cardiac NBCe1 overexpression exerts a direct effect on ventricular electrical activity

CARLOS A. VALVERDE; CAROLINA JAQUENOD DE GIUSTI; ROMINA DI MATTIA; PAULA BLANCO; ERNESTO ALEJANDRO AIELLO; LEANDRO AGUSTIN DIAZ ZEGARRA; ENRIQUE L. PORTIANSKY; ALEJANDRO ORLOWSKI

Buenos Aires

Congreso; Reunion Anula de Sociedades de Biociencia SAIC-SAI-SAFIS 2020; 2020

Introduction: Intracellular pH maintenance in cardiomyocytes is crucial for the correct function of electrical activity and contractility. Prevention of acidosis relies on two sarcolemmal acid extruders: Na+/H+ exchanger and Na+/HCO3- cotransporter (NBC). There are two known cardiac isoforms of NBC, an electroneutral NBCn1 and an electrogenic NBCe1, (1Na+:2HCO3-). We have previously demonstrated in rat and cat ventricular myocytes the existence of an anionic current generated by NBCe1 that contributes to the cardiac action potential shape and duration.Aim: The principal aim of this research was to determine the contribution of NBCe1 in heart electrophysiology in an in vivo mouse model with NBCe1 overexpression.Experimental design: We attempted NBCe1 overexpression by using a cardiotropic adenoassociated virus vector (AAV9-NBCe1) delivered through a retro-orbital injection in male 3 months old mice and then performed a series of studies to assess ventricular electrical activity including patch clamp technique on isolated cardiomyocytes and electrocardiogram (ECG), using an AAV9-mCherry as control. Results: We performed ECG studies on both mice groups before and after 28 days virus injection and we found a significant reduction in QTc interval duration of AAV9-NBCe1 injected mice compared to control, that was achieved after 14 days of treatment and sustained through time (ms; AAV9-mCherry:61.2±2.4,n=5;AAV9-NBCe1*:53.8±0.5,n=6;*p