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M. F. Romero, A. Sindic, M.-H. Chang, C. R. Sussman, C. Plata, A.-P. Chan, D. B. Mount, C. K. Bahler, M. P. Fautsch; Slc4 and Slc26 Bicarbonate Transporter Function and Localization in the Eye. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3628.
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Physiologically, bicarbonate transporters are important for control of both intra- and extra-cellular pH. The renal electrogenic Na+/HCO3- cotransporter (NBCe1/Slc4a4) is the major acid-base transporter allowing the kidneys to reclaim filtered HCO3-. Mutations in human NBCe1 result in severe renal disease (metabolic acidosis) and eye pathophysiology (cataracts, glaucoma). The SLC26 gene family is an anion (Cl-, I-, SO42-, oxalate, formate) transporter / channel family which was recently found to encode HCO3- transporters. Most of the Slc26 proteins are localized to apical epithelial membranes. Several members display novel activities not previously recognized in physiology, i.e., electrogenic Cl--nHCO3- exchange and electrogenic nCl--HCO3- exchange. We sought to determine where in the eye these proteins are and what is their function.
To understand NBCe1 (Slc4) and Slc26 physiology in the eye, we (a) localized the mRNA and protein in eyes of zebrafish, Xenopus, mice and humans; and (b) tested the function of human proteins & mutations. Function was accessed by expression of recombinant protein in Xenopus oocytes and activity monitored using ion selective microelectrodes.
Recessive NBCe1 mutations result in loss of membrane protein or decreased protein function. One Slc26 member, Slc26a9, is a new type of Na+ coupled HCO3- transporter and has at least two other transport modes: Cl--HCO3- exchanger and anion channel. Slc26a9 mRNA and protein is also in the eye. NBCe1 localizes to the basolateral membrane of the renal proximal tubule, while Slc26a9 is found in the apical membrane of these same cells. In the eye, NBCe1 protein distribution differs between species, with human being different from even mouse. NBCe1 is found in the corneal epithelia, ciliary body, trabecular meshwork, retinal pigmented epithelia and throughout the retina. Thusfar, we have found Slc26a9 only in corneal epithelia in the eye.
Both NBCe1 and Slc26a9 are found in the eye. The details of their function, will enable us to understand salt and fluid transport in the kidney and the eye.
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