title: Two-pore-domain potassium channels in smooth muscles: new components of myogenic regulation.
abstract: Gastrointestinal (GI) smooth muscles are influenced by many levels of regulation, including those provided by enteric motor neurones, hormones and paracrine substances. The integrated contractile responses to these regulatory mechanisms depend heavily on the state of excitability of smooth muscle cells. Resting ionic conductances and myogenic responses to agonists and physical parameters, such as stretch, are important in establishing basal excitability. This review discusses the role of 2-pore-domain K+ channels in contributing to background conductances and in mediating responses of GI muscles to enteric inhibitory nerve stimulation and stretch. Murine GI muscles express TREK-1 channels and display a stretch-dependent K+ (SDK) conductance that is also activated by nitric oxide via a cGMP-dependent mechanism. Cloning and expression of mTREK-1 produced an SDK conductance that was activated by cGMP-dependent phosphorylation at serine-351. GI muscle cells also express TASK-1 and TASK-2 channels that are inhibited by lidocaine and external acidification. These conductances appear to provide significant background K+ permeability that contributes to the negative resting potentials of GI muscles.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA. kent@unr.edu
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000818:Animals; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*
chemical_list: C498739:Kcnk5 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D011188:Potassium