ID | 111469 |
Author |
Hayashi, Mikio
Kansai Medical University
Matsuda, Hiroko
Kansai Medical University
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Keywords | pancreatic duct
potassium channel
patch clamp
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Content Type |
Others
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Description | 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.
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Journal Title |
The Journal of Medical Investigation
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ISSN | 13496867
13431420
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NCID | AA11166929
AA12022913
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Publisher | Faculty of Medicine Tokushima University
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Volume | 56
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Issue | Supplement
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Start Page | 354
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End Page | 354
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Sort Key | 354
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Published Date | 2009-12
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DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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