タイトル（掲載誌）The Journal of Medical Investigation
一般注記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.
一次資料へのリンクURLhttps://repo.lib.tokushima-u.ac.jp/files/public/11/111469/20180426144144254744/jmi_56_suppl_354.pdf
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）