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SLC4A11 is an EIPA-sensitive Na+ permeable pHi Regulator

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AJP Cell Physiology

Published online on

Abstract

SLC4A11, a member of the Solute Linked Cotransporter 4 family that is comprised predominantly of bicarbonate transporters, was described as an electrogenic 2Na+/ B(OH)4- (Borate) cotransporter and a Na+/ 2OH- cotransporter. The goal of the current study was to confirm and/or clarify the function of SLC4A11. In HEK293 cells transfected with SLC4A11 we tested if SLC4A11 is a: 1) Na+:HCO3- cotransporter, 2) Na+:OH- (H+) transporter, and/or 3) Na+:B(OH)4- cotransporter. CO2/HCO3-perfusion yielded no significant differences in rate or extent of pHi changes or Na+ flux in SLC4A11-transfected compared to control cells. Similarly, in CO2/HCO3-, acidification on removal of Na+ and alkalinization on Na+ add-back were not significantly different between control and transfected indicating that SLC4A11 does not have Na+:HCO3- cotransport activity. In the absence of CO2/HCO3-, SLC4A11-transfected cells showed higher resting [Na+i] (25 vs 17 mM), increased NH4+ induced acidification and increased acid recovery rate (160%) after an NH4 pulse. Na+ efflux and influx were faster (80%) following Na+ removal and add-back, respectively indicative of Na+:OH- (H+) transport by SLC4A11. The increased alkalinization recovery was confirmed in NHE-deficient PS120 cells demonstrating that SLC4A11 is a bonafide Na+:OH- (H+) transporter and not an activator of NHEs. SLC4A11 mediated H+ efflux is inhibited by EIPA (EC50: 0.1 µM). The presence of 10 mM borate did not alter dpHi/dt or pH during a Na+-free pulse in SLC4A11-transfected cells. In summary our results show that SLC4A11 is not a bicarbonate or borate-linked transporter, but has significant EIPA-sensitive Na+: OH- (H+) and NH4+ permeability.