2017年3月
Bicarbonate-rich fluid secretion predicted by a computational model of guinea-pig pancreatic duct epithelium
JOURNAL OF PHYSIOLOGY-LONDON
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- 巻
- 595
- 号
- 6
- 開始ページ
- 1947
- 終了ページ
- 1972
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1113/JP273306
- 出版者・発行元
- WILEY
A computational model of guinea-pig pancreatic duct epithelium was developed to determine the transportmechanism by whichHCO(3)(-)ions are secretedat concentrations inexcess of 140mM. Parameters defining the contributions of the individual ion channels and transporters were estimated by least-squares fitting of the model predictions to experimental data obtained from isolated ducts and intact pancreas under a range of experimental conditions. The effects of cAMP-stimulated secretion were well replicated by increasing the activities of the basolateral Na+-HCO(3)(-)cotransporter (NBC1) and apical Cl-/HCO(3)(-)exchanger (solute carrier family 26 member A6; SLC26A6), increasing the basolateral K+ permeability and apical Cl(-)and HCO(3)(-)permeabilities (CFTR), and reducing the activity of the basolateral Cl-/HCO(3)(-)exchanger (anion exchanger 2; AE2). Under these conditions, the model secreted similar to 140 mM HCO(3)(-)at a rate of similar to 3 nl min(-1) mm(-2), which is consistent with experimental observations. Alternative 1: 2 and 1: 1 stoichiometries for Cl-/HCO(3)(-)exchange via SLC26A6 at the apical membrane were able to support a HCO3--rich secretion. Raising the HCO3-/Cl(-)permeability ratio of CFTR from 0.4 to 1.0 had little impact upon either the secreted HCO(3)(-)concentration or the volume flow. However, modelling showed that a reduction in basolateral AE2 activity by similar to 80% was essential in minimizing the intracellular Cl(-)concentration following cAMP stimulation and thereby maximizing the secreted HCO(3)(-)concentration. The addition of a basolateral Na+-K+-2Cl(-)cotransporter (NKCC1), assumed to be present in rat and mouse ducts, raised intracellular Cl- and resulted in a lower secreted HCO3- concentration, as is characteristic of those species. We conclude therefore that minimizing the driving force for Cl- secretion is the main requirement for secreting 140 mM HCO3-.
- リンク情報
- ID情報
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- DOI : 10.1113/JP273306
- ISSN : 0022-3751
- eISSN : 1469-7793
- PubMed ID : 27995646
- Web of Science ID : WOS:000398116000015