ID 111469
著者
Hayashi, Mikio Kansai Medical University
Matsuda, Hiroko Kansai Medical University
キーワード
pancreatic duct
potassium channel
patch clamp
資料タイプ
その他
抄録
The ductal system of the exocrine pancreas produces HCO3--rich fluid in response to secretin and other stimuli. HCO3- efflux across the luminal membrane is mediated by a Cl--HCO3- exchanger operating in parallel with the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Basolateral K+ channels provide an exit pathway for K+ and play a vital role in maintaining the membrane potential, which is a crucial component of the driving force for anion secretion. Measurements of membrane potential with intracellular microelectrodes suggested that Ba2+-sensitive K+ conductance accounts for more than 60% of the total basolateral ionic conductance in resting ducts (1). To identify the Ba2+-sensitive K+ channels, we isolated ducts from normal rat pancreas by collagenase digestion. We first demonstrated that the ducts did not express a vascular endothelial marker PECAM-1 (platelet/endothelial cell adhesion molecule-1), but expressed cytokeratin 20, a marker of duct cells (2), using immunofluorescent staining. In addition, monoclonal anti-CFTR antibody was detected near the luminal membrane of these cells. In cell-attached single-channel recordings, we observed three types of K+ channels on basolateral membrane in unstimulated duct cells. The 40 pS K+ channels are likely to mediate whole-cell inwardly rectifying K+ (Kir) currents, which were blocked by extracellular Ba2+ in a voltage-dependent manner. The properties of 90 pS and 170 pS K+ channels are similar to those of Ca2+-activated K+ channels. We then identified Kir2.0 and SK4/IK1 (intermediate conductance Ca2+-activated K+ channel) subunits as molecular candidates of the K+ channels using RT-PCR analysis. The present results suggest that these subunits may mediate native K+ currents in resting duct cells. Further functional studies with specific blockers are required to evaluate which of these K+ channels contribute to the resting membrane potential and might be involved in HCO3- secretion.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
56
Supplement
開始ページ
354
終了ページ
354
並び順
354
発行日
2009-12
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版