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

Cited 23 time in Web of Science Cited 25 time in Scopus
Authors
Cho, Sang Yun; Beckett, Elizabeth A; Baker, Salah A; Han, Insoo; Park, Kyu Joo; Monaghan, Kevin; Ward, Sean M; Sanders, Kenton M; Koh, Sang Don
Issue Date
2005-03-19
Publisher
Blackwell Publishing
Citation
J Physiol. 2005 May 15;565(Pt 1):243-59. Epub 2005 Mar 17
Keywords
AnimalsCells, CulturedElectric ConductivityGastrointestinal Tract/physiologyHydrogen-Ion ConcentrationIntestines/chemistry/*physiologyIon Channel Gating/*physiologyMembrane Potentials/physiologyMiceMice, Inbred BALB CMuscle Cells/chemistry/*physiologyNerve Tissue Proteins/chemistry/*metabolismOocytes/physiologyPotassium/*metabolismPotassium Channels, Tandem Pore Domain/chemistry/*metabolismXenopus laevis
Abstract
The 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.
ISSN
0022-3751 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15774516

http://hdl.handle.net/10371/15576
DOI
https://doi.org/10.1113/jphysiol.2005.084574
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College of Medicine/School of Medicine (의과대학/대학원)Surgery (외과학전공)Journal Papers (저널논문_외과학전공)
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