Characterization of SLC26A9, facilitation of Cl(-) transport by bicarbonate

Cell Physiol Biochem. 2008;22(1-4):15-30. doi: 10.1159/000149780. Epub 2008 Jul 25.

Abstract

SLC26 family members are anionic transporters involved in Cl(-) and HCO(3)(-) absorption or secretion in epithelia. SLC26A9, preferentially expressed in the lung, is a poorly characterized member of this family. In this study, we investigated the transport properties of human SLC26A9 to determine its functional and pharmacological characteristics. SLC26A9 protein expression results in the appearance of an anionic current exhibiting an apparently linear current/voltage relationship and increases in (36)Cl influxes and effluxes. The sequences of conductivity, Cl(-) >I(-) > NO(3)(-) >/= gluconate > SO(4) (2-) and selectivity (P(x)/P(CI)), I(-) > NO(3)(-) > Cl(-) > gluconate > SO(4)(2-) are found. Cl(-) channel inhibitors DIDS and NS 3623 inhibit SLC26A9 associated currents while the specific CFTR inhibitor (CFTR(inh)-172) or glybenclamide has little effect. Elevation of intracellular cAMP (a CFTR activator) is also ineffective whereas increasing intracellular calcium blocks the SLC26A9 associated currents. The HCO(3)(-) conductance mediated by the SLC26A9 protein expression is low and no intracellular pHi changes are detectable under conditions favoring a Cl(-)/HCO(3)(-) exchange. However, the presence of HCO(3)(-)/CO(2) stimulates the Cl(-)-transporting activity of SLC26A9 in Xenopus laevis oocytes or SLC26A9-transduced COS-7 cells. As an important initial step in characterizing SLC26A9 function, we conclude that SLC26A9 is a Cl(-) channel and we suggest that HCO(3)(-) acts as a modulator of the channel. SLC26A9 physiological role in airway epithelia and its potential interaction with CFTR remain to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Bicarbonates / metabolism*
  • COS Cells
  • Calcium Signaling / drug effects
  • Chloride Channels / metabolism
  • Chloride-Bicarbonate Antiporters / metabolism
  • Chlorides / metabolism*
  • Chlorocebus aethiops
  • Gene Expression Regulation / drug effects
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Ion Channel Gating / drug effects
  • Ion Transport / drug effects
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Permeability / drug effects
  • RNA, Complementary / metabolism
  • Sulfate Transporters
  • Transduction, Genetic
  • Xenopus

Substances

  • Antiporters
  • Bicarbonates
  • Chloride Channels
  • Chloride-Bicarbonate Antiporters
  • Chlorides
  • RNA, Complementary
  • SLC26A9 protein, human
  • Sulfate Transporters
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid