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

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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.
LanguageEnglish
Pages957-964
Number of pages8
JournalCirculation Research
Volume93
DOIs
Publication statusPublished - 2003

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Membrane Potentials
Pulmonary Artery
Smooth Muscle Myocytes
Lung
Blood Vessels
4-Aminopyridine
Tetraethylammonium
Quinine
Halothane
Acidosis
Vasoconstriction
Ion Channels
Smooth Muscle
Cell Membrane
Rabbits
Messenger RNA

Keywords

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

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
Gurney, A.M. ; Osipenko, O.N. ; MacMillan, D. ; McFarlane, K.M. ; Tate, R.J.S.J. ; Kempsill, F.E.J. / Two-pore domain k channel, TASK-1, in pulmonary artery smooth muscle cells. In: Circulation Research. 2003 ; Vol. 93. pp. 957-964.
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Two-pore domain k channel, TASK-1, in pulmonary artery smooth muscle cells. / Gurney, A.M.; Osipenko, O.N.; MacMillan, D.; McFarlane, K.M.; Tate, R.J.S.J.; Kempsill, F.E.J.

In: Circulation Research, Vol. 93, 2003, p. 957-964.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Two-pore domain k channel, TASK-1, in pulmonary artery smooth muscle cells

AU - Gurney, A.M.

AU - Osipenko, O.N.

AU - MacMillan, D.

AU - McFarlane, K.M.

AU - Tate, R.J.S.J.

AU - Kempsill, F.E.J.

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N2 - 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.

AB - 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.

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KW - smooth muscle cells

KW - two-pore domain

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DO - 10.1161/01.RES.0000099883.68414.61

M3 - Article

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SP - 957

EP - 964

JO - Circulation Research

T2 - Circulation Research

JF - Circulation Research

SN - 0009-7330

ER -