title: HCO3- Transport through Anoctamin/Transmembrane Protein ANO1/TMEM16A in Pancreatic Acinar Cells Regulates Luminal pH.
abstract: The identification of ANO1/TMEM16A as the likely calcium-dependent chloride channel of exocrine glands has led to a more detailed understanding of its biophysical properties. This includes a calcium-dependent change in channel selectivity and evidence that HCO3 (-) permeability can be significant. Here we use freshly isolated pancreatic acini that preserve the luminal structure to measure intraluminal pH and test the idea that ANO1/TMEM16A contributes to luminal pH balance. Our data show that, under physiologically relevant stimulation with 10 pm cholesystokinin, the luminal acid load that results from the exocytic fusion of zymogen granules is significantly blunted by HCO3 (-) buffer in comparison with HEPES, and that this is blocked by the specific TMEM16A inhibitor T16inh-A01. Furthermore, in a model of acute pancreatitis, we observed substantive luminal acidification and provide evidence that ANO1/TMEM16A acts to attenuate this pH shift. We conclude that ANO1/TMEM16A is a significant pathway in pancreatic acinar cells for HCO3 (-) secretion into the lumen.
authors: From the School of Biomedical Sciences and.
authors: Yanfeng
authors: Y
authors: Han
authors: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia and.
authors: Annette M
authors: AM
authors: Shewan
authors: From the School of Biomedical Sciences and the Charles Perkins Centre, John Hopkins Drive, University of Sydney, Sydney, New South Wales 2050, Australia p.thorn@sydney.edu.au.
authors: Peter
authors: P
authors: Thorn
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000075369:Anoctamin-1; D001639:Bicarbonates / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D001639:Bicarbonates; D018118:Chloride Channels
keywords: bicarbonate; epithelial cell; exocytosis; ion channel; pancreas; secretion; transporter