科研之友
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摘要
Song Y, Yamamoto A, Steward MC, Ko SB, Stewart AK, Soleimani M, Liu BC, Kondo T, Jin CX, Ishiguro H. Deletion of Slc26a6 alters the stoichiometry of apical Cl-/HCO3- exchange in mouse pancreatic duct. Am J Physiol Cell Physiol 303: C815-C824, 2012. First published August 15, 2012; doi:10.1152/ajpcell.00151.2012.-To define the stoichiometry and molecular identity of the Cl-/HCO3- exchanger in the apical membrane of pancreatic duct cells, changes in luminal pH and volume were measured simultaneously in interlobular pancreatic ducts isolated from wild-type and Slc26a6-null mice. Transepithelial fluxes of HCO3- and Cl- were measured in the presence of anion gradients favoring rapid exchange of intracellular HCO3- with luminal Cl- in cAMP-stimulated ducts. The flux ratio of Cl- absorption/HCO3- secretion was similar to 0.7 in wild-type ducts and similar to 1.4 in Slc26a6(-/-) ducts where a different Cl-/HCO3- exchanger, most likely SLC26A3, was found to be active. Interactions between Cl-/HCO3- exchange and cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated ducts were examined by measuring the recovery of intracellular pH after alkali-loading by acetate prepulse. Hyperpolarization induced by luminal application of CFTRinh-172 enhanced HCO3- efflux across the apical membrane via SLC26A6 in wild-type ducts but significantly reduced HCO3- efflux in Slc26a6(-/-) ducts. In microperfused wild-type ducts, removal of luminal Cl-, or luminal application of dihydro-4,4%26apos;-diisothiocyanatostilbene-2,2%26apos;-disulphonic acid to inhibit SLC26A6, caused membrane hyperpolarization, which was abolished in Slc26a6(-/-) ducts. In conclusion, we have demonstrated that deletion of Slc26a6 alters the apparent stoichiometry of apical Cl-/HCO3- exchange in native pancreatic duct. Our results are consistent with SLC26A6 mediating 1:2 Cl-/HCO3- exchange, and the exchanger upregulated in its absence, most probably SLC26A3, mediating 2:1 exchange.
- 出版日期2012-10
- 单位吉林大学
