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(Circulation Research. 2003;93:957.)
© 2003 American Heart Association, Inc.

Cellular Biology

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

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

From the Department of Physiology and Pharmacology (A.M.G., R.J.T.), University of Strathclyde, Glasgow, UK; Quintiles Scotland Ltd (O.N.O., K.M.M.), Heriot-Watt University Research Park, Edinburgh, UK; Institute of Biomedical and Life Sciences (D.M.), University of Glasgow, Glasgow, UK; Argyll and Clyde NHS (F.E.J.K.), Royal Alexandra Hospital, Paisley, UK.

Correspondence to Prof Alison M. Gurney, Department of Physiology and Pharmacology, University of Strathclyde, 27 Taylor St, Glasgow, UK G4 0NR. E-mail a.m.gurney{at}strath.ac.uk

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 (I_KN), 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 I_KN and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover, I_KN 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 Ca²⁺. These properties are all diagnostic of TASK-1 channels and add to previously identified features of I_KN 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.

Key Words: two-pore domain K channel • pulmonary artery myocyte • smooth muscle • resting potential

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