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This Article Full Text Full Text (PDF) All Versions of this Article: 581/1/33    most recent jphysiol.2007.128389v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Parker, M. D. Articles by Tanner, M. J. A. Search for Related Content PubMed PubMed Citation Articles by Parker, M. D. Articles by Tanner, M. J. A. Related Collections Molecular and Genomic

Department of
¹ Biochemistry
² Physiology, University of Bristol, University Walk, Bristol, BS8 1TD, UK
³ Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA

Human red cell anion exchanger AE1 (band 3) is an electroneutral Cl–HCO₃^– exchanger with 12–14 transmembrane spans (TMs). Previous work using Xenopus oocytes has shown that two co-expressed fragments of AE1 lacking TMs 6 and 7 are capable of forming a stilbene disulphonate-sensitive ³⁶Cl-influx pathway, reminiscent of intact AE1. In the present study, we create a single construct, AE1(6: 7), representing the intact protein lacking TMs 6 and 7. We expressed this construct in Xenopus oocytes and evaluated it employing a combination of two-electrode voltage clamp and pH-sensitive microelectrodes. We found that, whereas AE1(6: 7) has some electroneutral Cl–base exchange activity, the protein also forms a novel anion-conductive pathway that is blocked by DIDS. The mutation Lys₅₃₉Ala at the covalent DIDS-reaction site of AE1 reduced the DIDS sensitivity, demonstrating that (1) the conductive pathway is intrinsic to AE1(6: 7) and (2) the conductive pathway has some commonality with the electroneutral anion-exchange pathway. The conductance has an anion-permeability sequence: NO₃^– I^– > NO₂^– > Br^– > Cl^– > SO₄^2– HCO₃^– gluconate^– aspartate^– cyclamate^–. It may also have a limited permeability to Na⁺ and the zwitterion taurine. Although this conductive pathway is not a usual feature of intact mammalian AE1, it shares many properties with the anion-conductive pathways intrinsic to two other Cl–HCO₃^– exchangers, trout AE1 and mammalian SLC26A7.

(Received 16 January 2007; accepted after revision 20 February 2007; first published online 22 February 2007)
Corresponding author: Mark D. Parker, Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, SHM B-127, New Haven, CT 06510, USA. Email: mark.parker{at}yale.edu