SLC4A11 is an EIPA-sensitive Na+ permeable pHi regulator

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 with 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 CO3/HCO3 -, SLC4A11-transfected cells showed higher resting intracelllular Na+ concentration ([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 5-(N-ethyl-Nisopropyl) amiloride (EIPA; EC50: 0.1 μM). The presence of 10 mM borate did not alter dpHi/dt or ΔpH 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. © 2013 by the American Physiological Society.