Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract|
|Citation:||Journal of Physiology-London, 2005; 565(1):243-259|
|Publisher:||Blackwell Publishing Ltd|
|Sang 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|
|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.|
|Keywords:||Gastrointestinal Tract; Intestines; Oocytes; Cells, Cultured; Muscle Cells; Animals; Mice, Inbred BALB C; Xenopus laevis; Mice; Potassium; Potassium Channels, Tandem Pore Domain; Nerve Tissue Proteins; Ion Channel Gating; Membrane Potentials; Electric Conductivity; Hydrogen-Ion Concentration|
|Description:||Published online before print March 17, 2005. The definitive version is available at www.blackwell-synergy.com|
|Rights:||Copyright © 2005 The Physiological Society.|
|Appears in Collections:||Molecular and Biomedical Science publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.