CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
Involvement of AE3 isoform of Na+-independent Cl/HCO3 exchanger in myocardial pHi recovery from intracellular alkalization.
CHIAPPE DE CINGOLANI GE; ENNIS IL; MORGAN PE; ALVAREZ BV; CASEY JR; CAMILIÓN DE HURTADO MC
Año: 2006 p. 3018 - 3026
Myocardial pHi recovery from intracellular alkalization results in part from the acid load (−JH+) carried by Cl−/HCO3 − anion-exchangers (AE). Three AE isoforms, AE1, AE2 and AE3, have been identified in cardiac membranes, but the function of each isoform on pHi homeostasis is still under investigation. This work explored, by means of specific antibodies, the role of AE3 isoform in myocardial pHi regulation. We developed rabbit polyclonal antibodies against the extracellular loops: one connecting the fifth to sixth and the other one the seventh to eighth transmembrane domains (loops 3 and 4, respectively) of AE3, and their effect on pHi regulation was studied in rat papillary muscles. The anti-AE3 loop 3 antibody decreased −JH+ in response to myocardial alkalization (from a mean control value of 1.06±0.26 to 0.32±0.13 mmol/L/min, n=7, P< 0.05) without affecting the baseline pHi (7.22±0.03 vs. 7.21±0.04). The anti-AE3 loop 4 antibody did not modify either pHi recovery or baseline pHi. Under control conditions, endothelin-1 (ET-1) increased −JH+ in response to myocardial alkalization from 1.30±0.18 to 2.01±0.33 mmol/L /min (n=5, P< 0.05). This effect of ET-1 on −JH+ was abolished by anti-AE3 loop 3 antibody. In addition, the MgATP-induced stimulation of AE activity was reduced by the anti-AE3 loop 3 antibody. These data support the key role of the AE3 isoform in myocardial pHi recovery from alkaline loads and also in the stimulatory effect of ET-1 on AE activity. To a lesser extent, it may also contribute to the effect of MgATP on pHi.