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Electrophysiological changes in Slc26a3 (down‐regulated in adenoma, Dra) knockout intestine are associated with epithelial cell alkalinity
Author(s) -
Clarke Lane L,
Horak R Zachary,
Simpson Janet E,
Walker Nancy M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.799.6
Subject(s) - ussing chamber , depolarization , chemistry , apical membrane , transepithelial potential difference , extracellular , intracellular ph , epithelial polarity , biophysics , membrane potential , ion transporter , small intestine , cotransporter , intracellular , electrophysiology , biochemistry , biology , medicine , sodium , membrane , secretion , organic chemistry
Dra is the major apical membrane anion exchanger in the small and large intestine. Studies of recombinant DRA have proposed an electrogenic 2Cl − :1HCO 3 − stoichiometry ( J. Gen. Physiol. 127: 511, 2006). However, in Dra knockout mice (DraKO) loss of Cl − absorption is associated with only small increases in transepithelial short‐circuit current (I sc ). To investigate the electrophysiological changes resulting from loss of Dra, microelectrode analysis, intracellular pH (pH i ) microfluorimetry and Ussing chamber studies were performed on DraKO and wild‐type (WT) intestine. Microelectrode studies revealed that the apical membrane potential (V a ) of cecal epithelium was paradoxically greater in the DraKO and V a depolarization induced by extracellular Cl − (Cl − o ) removal was not different than WT. Studies of cystic fibrosis mouse intestine indicated that V a depolarization during Cl − o removal was CFTR dependent and eliminated by high [K + ]. Microfluorimetry studies revealed alkaline pH i in DraKO small and large intestinal epithelia. Ussing chamber experiments of DraKO small intestine found that increased I sc was abolished by epithelial acidification. We conclude that intestinal Dra demonstrates an electroneutral stoichiometry (e.g., 1Cl − :1HCO 3 − ) and that increased I sc in DraKO intestine is associated with epithelial alkalinity that may activate basolateral membrane K + channels. Support: NIDDK and CFF.