Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH.
The SLC4A11 gene encodes the bicarbonate-transporter-related protein BTR1, which is mutated in syndromes characterized by vision and hearing loss. Signs of these diseases [congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome] are evident in mouse models of Slc4a11 disruption. However, the intrinsic activity of Slc4a11 remains controversial, complicating assignment of its (patho)physiological role. Most studies concur that Slc4a11 transports H+(or the thermodynamically equivalent species OH-) rather than HCO3-, but disparities have arisen as to whether the transport is coupled to another species such as Na+or NH3/NH4+Here for the first time, we examine the action of mouse Slc4a11 in Xenopus oocytes. We simultaneously monitor changes in intracellular pH, membrane potential, and conductance as we alter extracellular pH, revealing the electrical and chemical driving forces that underlie the observed ion fluxes. We find that mSlc4a11 is an ideally selective H+/OH-conductive pathway, the action of which is uncoupled from the cotransport of any other ion. We also find that the activity of mSlc4a11 is independently enhanced by both extracellular and intracellular alkalinization, suggesting OH-as the most likely substrate and providing a novel explanation for the apparent NH3-dependence of Slc4a11-mediated currents reported by others. We suggest that the unique properties of Slc4a11 action underlie its value as a pH regulator in corneal endothelial cells.
Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, New York.
Evan J
EJ
Myers
Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, New York.
Aniko
A
Marshall
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Michael L
ML
Jennings
Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, New York; parker28@buffalo.edu.|Department of Ophthalmology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo: The State University of New York, Buffalo, New York; and.|State University of New York Eye Institutes, University at Buffalo: The State University of New York, Buffalo, New York.
Mark D
MD
Parker
D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*
D027321:Anion Transport Proteins; D017920:Antiporters; D001639:Bicarbonates; D006878:Hydroxides; C544607:Slc4a11 protein, mouse; D027981:Symporters; C031356:hydroxide ion; D012964:Sodium
NaBC1; acid-base; cornea; fluid transport; proton
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