Two-Pore Domain K Channel, TASK-1, in Pulmonary Artery Smooth Muscle Cells

Alison M. Gurney, O. N. Osipenko, D. MacMillan, K. M. McFarlane, R. J. Tate, F. E J Kempsill

    Research output: Contribution to journalArticlepeer-review


    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 μmol/L) and anandamide (10 μmol/L), but insensitive to cytoplasmic Ca 2+. 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.
    Original languageEnglish
    Pages (from-to)957-964
    Number of pages7
    JournalCirculation research
    Issue number10
    Publication statusPublished - 14 Nov 2003


    • Pulmonary artery myocyte
    • Resting potential
    • Smooth muscle
    • Two-pore domain K channel


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