A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract

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dc.contributor.authorCho, S.
dc.contributor.authorSpencer, E.
dc.contributor.authorBaker, S.
dc.contributor.authorHan, I.
dc.contributor.authorPark, K.
dc.contributor.authorMonaghan, K.
dc.contributor.authorWard, S.
dc.contributor.authorSanders, K.
dc.contributor.authorKoh, S.
dc.date.issued2005
dc.descriptionPublished online before print March 17, 2005. The definitive version is available at www.blackwell-synergy.com
dc.description.abstractThe excitability of smooth muscles is regulated, in part, by background K+ conductances that determine resting membrane potential. However, the K+ conductances so far described in gastrointestinal (GI) muscles are not sufficient to explain the negative resting potentials of these cells. Here we describe expression of two-pore K+ channels of the TASK family in murine small and large intestinal muscles. TASK-2, cloned from murine intestinal muscles, resulted in a pH-sensitive, time-dependent, non-inactivating K+ conductance with slow activation kinetics. A similar conductance was found in native intestinal myocytes using whole-cell patch-clamp conditions. The pH-sensitive current was blocked by local anaesthetics. Lidocaine, bupivacaine and acidic pH depolarized circular muscle cells in intact muscles and decreased amplitude and frequency of slow waves. The effects of lidocaine were not blocked by tetraethylammonium chloride, 4-aminopyridine, glibenclamide, apamin or MK-499. However, depolarization by acidic pH was abolished by pre-treatment with lidocaine, suggesting that lidocaine-sensitive K+ channels were responsible for pH-sensitive changes in membrane potential. The kinetics of activation, sensitivity to pH, and pharmacology of the conductance in intestinal myocytes and the expression of TASK-1 and TASK-2 in these cells suggest that the pH-sensitive background conductance is encoded by TASK genes. This conductance appears to contribute significantly to resting potential and may regulate excitability of GI muscles.
dc.description.statementofresponsibilitySang Yun Cho, Elizabeth A. Beckett, Salah A. Baker, Insoo Han, Kyu Joo Park, Kevin Monaghan, Sean M. Ward, Kenton M. Sanders and Sang Don Koh
dc.identifier.citationJournal of Physiology, 2005; 565(1):243-259
dc.identifier.doi10.1113/jphysiol.2005.084574
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.urihttp://hdl.handle.net/2440/47318
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.rightsCopyright © 2005 The Physiological Society.
dc.source.urihttp://jp.physoc.org/cgi/reprint/565/1/243
dc.subjectGastrointestinal Tract
dc.subjectIntestines
dc.subjectOocytes
dc.subjectCells, Cultured
dc.subjectMuscle Cells
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectXenopus laevis
dc.subjectMice
dc.subjectPotassium
dc.subjectPotassium Channels, Tandem Pore Domain
dc.subjectNerve Tissue Proteins
dc.subjectIon Channel Gating
dc.subjectMembrane Potentials
dc.subjectElectric Conductivity
dc.subjectHydrogen-Ion Concentration
dc.titleA pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract
dc.typeJournal article
pubs.publication-statusPublished

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