A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract.
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.
Cho
Sang Yun
SY
Department of Physiology and Cell Biology, University of Nevada Reno, School of Medicine, Reno, NV 89557, USA.
Beckett
Elizabeth A
EA
Baker
Salah A
SA
Han
Insoo
I
Park
Kyu Joo
KJ
Monaghan
Kevin
K
Ward
Sean M
SM
Sanders
Kenton M
KM
Koh
Sang Don
SD
D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D041981:Gastrointestinal Tract / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000737:chemistry / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D032342:Muscle Cells / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
C498739:Kcnk5 protein, mouse; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D011188:Potassium