Human SLC4A11 is a Novel NH3: H+ Co-transporter [Cell Biology]

May 27th, 2015 by Zhang, W., Ogando, D. G., Bonanno, J. A., Obukhov, A. G.

SLC4A11 has been proposed to be an electrogenic membrane transporter, permeable to Na+, H+ (OH-), bicarbonate, borate and NH4+. Recent studies indicate however, that neither bicarbonate nor borate are substrates. Here, we examined potential NH4+, Na+, and H+ contributions to electrogenic ion transport through SLC4A11 stably expressed in Na+/H+ exchanger-deficient PS120 fibroblasts. Inward currents observed during exposure to NH4Cl were determined by the [NH3]o not [NH4+]o and current amplitudes varied with the [H+] gradient. These currents were relatively unaffected by removal of Na+, K+, or Cl- from the bath, but could be reduced by inclusion of NH4Cl in the pipette solution. Bath pH changes alone did not generate significant currents through SLC4A11, except immediately following exposure to NH4Cl. Reversal potential shifts in response to changing [NH3]o and pHo suggested an NH3:H+ coupled transport mode for SLC4A11. Proton flux through SLC4A11 in the absence of ammonia was relatively small, suggesting ammonia transport is of more physiological relevance. Methyl-ammonia produced currents similar to NH3, but with reduced amplitude. Estimated stoichiometry of SLC4A11 transport was 1NH3:2H+. NH3 dependent currents were insensitive to 10 μM ethyl-isopropyl amiloride (EIPA) or 100 μM 4,4'- diisothiocyanatostilbene -2,2'-disulphonic acid (DIDS). We propose that SLC4A11 is an NH3:2H+ co-transporter exhibiting unique characteristics.