Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells.
Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca2+ influx, and contraction. The resting potential is determined largely by the activity of K+-selective ion channels, the molecular nature of which has been debated for some time. In this study, we provide strong evidence that the two-pore domain K+ channel, TASK-1, mediates a noninactivating, background K+ current (IKN), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs). TASK-1 mRNA was found to be present in PASMCs, and the membranes of PASMCs contained TASK-1 protein. Both IKN and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover, IKN and the resting potential were enhanced by halothane (1 mmol/L), inhibited by Zn2+ (100 to 200 micromol/L) and anandamide (10 micromol/L), but insensitive to cytoplasmic Ca2+. These properties are all diagnostic of TASK-1 channels and add to previously identified features of IKN that are shared with TASK-1, such as inhibition by hypoxia, low sensitivity to 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions. It is therefore concluded that TASK-1 channels are major contributors to the resting potential in pulmonary artery smooth muscle. They are likely to play an important role in mediating pulmonary vascular responses to changes in extracellular pH, and they could be responsible for the modulatory effects of pH on hypoxic pulmonary vasoconstriction.
Gurney
A M
AM
Department of Physiology and Pharmacology, University of Strathclyde, 27 Taylor St, Glasgow, UK G4 0NR. a.m.gurney@strath.ac.uk
Osipenko
O N
ON
MacMillan
D
D
McFarlane
K M
KM
Tate
R J
RJ
Kempsill
F E J
FE
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002469:Cell Separation; D003593:Cytoplasm / Q000378:metabolism; D063388:Endocannabinoids; D006221:Halothane / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015032:Zinc / Q000494:pharmacology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D009419:Nerve Tissue Proteins; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C420132:potassium channel subfamily K member 3; D015032:Zinc; D011188:Potassium; D002118:Calcium; D006221:Halothane; C078814:anandamide