Molecular characterization of the murine Slc26a6 anion exchanger: Functional comparison with Slc26a1

Qizhi Xie, Rick Welch, Adriana Mercado, Michael F Romero, David B. Mount

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

We report the molecular and functional characterization of murine Slc26a6, the putative apical chloride-formate exchanger of the proximal tubule. The Slc26a6 transcript is expressed in several tissues, including kidney. Alternative splicing of the second exon generates two distinct isoforms, denoted Slc26a6a and Slc26a6b, which differ in the inclusion of a 23-residue NH2-terminal extension. Functional comparison with murine Slc26a1, the basolateral oxalate exchanger of the proximal tubule, reveals a number of intriguing differences. Whereas Slc26a6 is capable of Cl-, SO4 2-, formate, and oxalate uptake when expressed in Xenopus laevis oocytes, Slc26a1 transports only SO4 2- and oxalate. Measurement of intracellular pH during the removal of extracellular Cl- in the presence and absence of HCO3 - indicates that Slc26a6 functions as both a Cl-/HCO3 - and a Cl-/OH- exchanger; simultaneous membrane hyperpolarization during these experimental maneuvers reveals that HCO3 - and OH- transport mediated by Slc26a6 is electrogenic. Cis-inhibition and efflux experiments indicate that Slc26a6 can mediate the exchange of both Cl- and SO4 2- with a number of substrates, including formate and oxalate. In contrast, SO4 2- and oxalate transport by Slc26a1 are mutually cis-inhibited but activated significantly by extracellular halides, lactate, and formate. The data indicate that Slc26a6 encodes an apical Cl-/formate/oxalate and Cl-/base exchanger and reveal significant mechanistic differences between apical and basolateral oxalate exchangers of the proximal tubule.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number4 52-4
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

formic acid
Oxalates
Anions
Xenopus laevis
Alternative Splicing
Oocytes
Chlorides
Exons
Lactic Acid
Protein Isoforms
Kidney

Keywords

  • Anion exchange
  • Chloride
  • Formate
  • Oxalate
  • Proximal tubule

ASJC Scopus subject areas

  • Physiology

Cite this

Molecular characterization of the murine Slc26a6 anion exchanger : Functional comparison with Slc26a1. / Xie, Qizhi; Welch, Rick; Mercado, Adriana; Romero, Michael F; Mount, David B.

In: American Journal of Physiology - Renal Physiology, Vol. 283, No. 4 52-4, 10.2002.

Research output: Contribution to journalArticle

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KW - Anion exchange

KW - Chloride

KW - Formate

KW - Oxalate

KW - Proximal tubule

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