A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract
Date
2005
Authors
Cho, S.
Spencer, E.
Baker, S.
Han, I.
Park, K.
Monaghan, K.
Ward, S.
Sanders, K.
Koh, S.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Physiology, 2005; 565(1):243-259
Statement of Responsibility
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
Conference Name
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.
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Description
Published online before print March 17, 2005. The definitive version is available at www.blackwell-synergy.com
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Copyright © 2005 The Physiological Society.