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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Membrane Physiology and Membrane Biophysics
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1440720
This article is part of the Research Topic Advances in Acid-Base Physiology: From Single Transporters to Physiology View all articles

NH 3 /NH 4 + allosterically activates SLC4A11 by causing an acidic shift in the intracellular pK that governs H + (OH -) conductance

Provisionally accepted
Richard A. Pasternack Richard A. Pasternack Bianca N. Quade Bianca N. Quade Aniko Marshall Aniko Marshall Mark D. Parker Mark D. Parker *
  • Physiology and Biophysics, University at Buffalo, Buffalo, NY, United States

The final, formatted version of the article will be published soon.

    SLC4A11 is the most abundant membrane transport protein in corneal endothelial cells. Its functional presence is necessary to support the endothelial fluid pump that draws fluid from the corneal stroma, preventing corneal edema. Several molecular actions have been proposed for SLC4A11 including H2O transport and cell adhesion. One of the most reproduced actions that SLC4A11 mediates is a H + (or OH -) conductance that is enhanced in the presence of NH4Cl. The mechanism by which this occurs is controversial with some providing evidence in favor of NH3-H + cotransport and others providing evidence for uncoupled H + transport that is indirectly stimulated by the effects of NH4Cl upon intracellular pH and membrane potential. In the present study we provide new evidence and revisit previous studies, to support a model in which NH4Cl causes direct allosteric activation of SLC4A11 by means of an acidic shift in the intracellular pK (pKi) that governs the relationship between intracellular pH (pHi) and SLC4A11 H + -conductance. These findings have important implications for the assignment of a physiological role for SLC4A11.

    Keywords: acid-base, Btr1, NaBC1, Cornea, proton

    Received: 29 May 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Pasternack, Quade, Marshall and Parker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mark D. Parker, Physiology and Biophysics, University at Buffalo, Buffalo, 14214, NY, United States

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