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J Physiol
2008 Mar 01;5865:1291-306. doi: 10.1113/jphysiol.2007.143222.
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Species differences in Cl- affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl- exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis.
Clark JS
,
Vandorpe DH
,
Chernova MN
,
Heneghan JF
,
Stewart AK
,
Alper SL
.
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The mouse is refractory to lithogenic agents active in rats and humans, and so has been traditionally considered a poor experimental model for nephrolithiasis. However, recent studies have identified slc26a6 as an oxalate nephrolithiasis gene in the mouse. Here we extend our earlier demonstration of different anion selectivities of the orthologous mouse and human SLC26A6 polypeptides to investigate the correlation between species-specific differences in SLC26A6 oxalate/anion exchange properties as expressed in Xenopus oocytes and in reported nephrolithiasis susceptibility. We find that human SLC26A6 mediates minimal rates of Cl(-) exchange for Cl(-), sulphate or formate, but rates of oxalate/Cl(-) exchange roughly equivalent to those of mouse slc2a6. Both transporters exhibit highly cooperative dependence of oxalate efflux rate on extracellular [Cl(-)], but whereas the K(1/2) for extracellular [Cl(-)] is only 8 mM for mouse slc26a6, that for human SLC26A6 is 62 mM. This latter value approximates the reported mean luminal [Cl(-)] of postprandial human jejunal chyme, and reflects contributions from both transmembrane and C-terminal cytoplasmic domains of human SLC26A6. Human SLC26A6 variant V185M exhibits altered [Cl(-)] dependence and reduced rates of oxalate/Cl(-) exchange. Whereas mouse slc26a6 mediates bidirectional electrogenic oxalate/Cl(-) exchange, human SLC26A6-mediated oxalate transport appears to be electroneutral. We hypothesize that the low extracellular Cl(-) affinity and apparent electroneutrality of oxalate efflux characterizing human SLC26A6 may partially explain the high human susceptibility to nephrolithiasis relative to that of mouse. SLC26A6 sequence variant(s) are candidate risk modifiers for nephrolithiasis.
Cao,
Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity.
2004, Pubmed
Cao,
Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity.
2004,
Pubmed
Chernova,
Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Chernova,
Functional comparison of mouse slc26a6 anion exchanger with human SLC26A6 polypeptide variants: differences in anion selectivity, regulation, and electrogenicity.
2005,
Pubmed
,
Xenbase
Coe,
Kidney stone disease.
2005,
Pubmed
Fordtran,
Ionic constituents and osmolality of gastric and small-intestinal fluids after eating.
1966,
Pubmed
Frassetto,
Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion.
2000,
Pubmed
Freel,
Conductive pathways for chloride and oxalate in rabbit ileal brush-border membrane vesicles.
1998,
Pubmed
Freel,
Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice.
2006,
Pubmed
Harris,
Serum oxalate in human beings and rats as determined with the use of ion chromatography.
2004,
Pubmed
Hatch,
Regulatory aspects of oxalate secretion in enteric oxalate elimination.
1999,
Pubmed
Hatch,
Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion.
2006,
Pubmed
Holmes,
Contribution of dietary oxalate to urinary oxalate excretion.
2001,
Pubmed
Hoppe,
Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.
2006,
Pubmed
Jennings,
Characterization of oxalate transport by the human erythrocyte band 3 protein.
1996,
Pubmed
Jiang,
Specificity of anion exchange mediated by mouse Slc26a6.
2002,
Pubmed
,
Xenbase
Jiang,
Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
2006,
Pubmed
Knickelbein,
Oxalate transport by anion exchange across rabbit ileal brush border.
1986,
Pubmed
Kuo,
Pathways for oxalate transport in rabbit renal microvillus membrane vesicles.
1996,
Pubmed
Lamprecht,
Transport properties of the human intestinal anion exchanger DRA (down-regulated in adenoma) in transfected HEK293 cells.
2005,
Pubmed
Martial,
Importance of several cysteine residues for the chloride conductance of trout anion exchanger 1 (tAE1).
2007,
Pubmed
,
Xenbase
Martial,
Consequences of point mutations in trout anion exchanger 1 (tAE1) transmembrane domains: evidence that tAE1 can behave as a chloride channel.
2006,
Pubmed
,
Xenbase
McMartin,
Calcium oxalate monohydrate, a metabolite of ethylene glycol, is toxic for rat renal mitochondrial function.
2005,
Pubmed
Mio,
The motor protein prestin is a bullet-shaped molecule with inner cavities.
2008,
Pubmed
Muldowney,
Dietary chloride and urinary calcium in stone disease.
1994,
Pubmed
Osswald,
Renal elimination kinetics and plasma half-life of oxalate in man.
1979,
Pubmed
Restrepo,
A novel method to differentiate between ping-pong and simultaneous exchange kinetics and its application to the anion exchanger of the HL60 cell.
1992,
Pubmed
Ribaya,
Factors affecting endogenous oxalate synthesis and its excretion in feces and urine in rats.
1982,
Pubmed
Schaechinger,
Nonmammalian orthologs of prestin (SLC26A5) are electrogenic divalent/chloride anion exchangers.
2007,
Pubmed
Shcheynikov,
Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6.
2006,
Pubmed
,
Xenbase
Soleimani,
The role of SLC26A6-mediated chloride/oxalate exchange in causing susceptibility to nephrolithiasis.
2008,
Pubmed
Stewart,
Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain.
2002,
Pubmed
,
Xenbase
Taylor,
Oxalate intake and the risk for nephrolithiasis.
2007,
Pubmed
Turnberg,
Mechanism of bicarbonate absorption and its relationship to sodium transport in the human jejunum.
1970,
Pubmed
Turnberg,
Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum.
1970,
Pubmed
Wesson,
Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules.
2003,
Pubmed
Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase
Yamakawa,
Oxalate:OH exchange across rat renal cortical brush border membrane.
1990,
Pubmed
Yamauchi,
Oxalate removal by daily dialysis in a patient with primary hyperoxaluria type 1.
2001,
Pubmed
Zheng,
Analysis of the oligomeric structure of the motor protein prestin.
2006,
Pubmed
