THE CARDIAC ELECTROGENIC SODIUM/BICARBONATE COTRANSPORTER (NBCe1) IS ACTIVATED BY ALDOSTERONE THROUGH THE G PROTEINCOUPLED RECEPTOR 30 (GPR30)

ORLOWSKI A,; DE GIUSTI VC; CIANCIO MC; ESPEJO M SOFIA; AIELLO EA.

CHANNELS

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2016

1933-6950

AbstractThe sodium/bicarbonate cotransporter (NBC) transports extracellular Na+ and HCO3- into the cytoplasm upon intracellular acidosis, restoring the acidic pHi to near neutral values. Two different NBC isoforms have been described in the heart, the electroneutral NBCn1 (1Na+:1HCO3 -) and the electrogenic NBCe1 (1Na+:2HCO3 -). Certain non-genomic effects of aldosterone (Ald) were due toan orphan G protein-couple receptor 30 (GPR30). We have recently demonstrated that Ald activates GPR30 in adult rat ventricular myocytes, which transactivates the epidermal growth factor receptor (EGFR) and in turn triggers a reactive oxygen species (ROS)- and PI3K/AKTdependent pathway, leading to the stimulation of NBC. The aim of this study was to investigate the NBC isoform involved in the Ald/GPR30-induced NBC activation. Using specific NBCe1 inhibitory antibodies (a-L3) we demonstrated that Ald does not affect NBCn1 activity. Ald was ableto increase NBCe1 activity recorded in isolation. Using immunofluorescence and confocal microscopy analysis we showed in this work that both NBCe1 and GPR30 are localized in t-tubules.In conclusion, we have demonstrated that NBCe1 is the NBC isoform activated by Ald in the heart.