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.S.J. Tate, F.E.J. Kempsill

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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 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.
Original languageEnglish
Pages (from-to)957-964
Number of pages8
JournalCirculation Research
Volume93
DOIs
Publication statusPublished - 2003

Keywords

  • pulmonary artery
  • smooth muscle cells
  • two-pore domain

Fingerprint Dive into the research topics of 'Two-pore domain k channel, TASK-1, in pulmonary artery smooth muscle cells'. Together they form a unique fingerprint.

  • Cite this

    Gurney, A. M., Osipenko, O. N., MacMillan, D., McFarlane, K. M., Tate, R. J. S. J., & Kempsill, F. E. J. (2003). Two-pore domain k channel, TASK-1, in pulmonary artery smooth muscle cells. Circulation Research, 93, 957-964. https://doi.org/10.1161/01.RES.0000099883.68414.61