| Autor: |
Orlowski A; a Centro de Investigaciones Cardiovasculares 'Dr. Horacio Cingolani' , Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET , La Plata , Buenos Aires , Argentina., De Giusti VC; a Centro de Investigaciones Cardiovasculares 'Dr. Horacio Cingolani' , Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET , La Plata , Buenos Aires , Argentina., Ciancio MC; a Centro de Investigaciones Cardiovasculares 'Dr. Horacio Cingolani' , Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET , La Plata , Buenos Aires , Argentina., Espejo MS; a Centro de Investigaciones Cardiovasculares 'Dr. Horacio Cingolani' , Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET , La Plata , Buenos Aires , Argentina., Aiello EA; a Centro de Investigaciones Cardiovasculares 'Dr. Horacio Cingolani' , Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET , La Plata , Buenos Aires , Argentina. |
| Abstrakt: |
The sodium/bicarbonate cotransporter (NBC) transports extracellular Na + and HCO 3 - into the cytoplasm upon intracellular acidosis, restoring the acidic pH i to near neutral values. Two different NBC isoforms have been described in the heart, the electroneutral NBCn1 (1Na + :1HCO 3 - ) and the electrogenic NBCe1 (1Na + :2HCO 3 - ). Certain non-genomic effects of aldosterone (Ald) were due to an 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/AKT-dependent 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 able to 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. |
