Potential role for kv3.1b channels as oxygen sensors

O N Osipenko, R J Tate, A M Gurney, Rothwelle Tate

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Hypoxia inhibits voltage-gated K channels in pulmonary artery smooth muscle (PASM). This is thought to contribute to hypoxic pulmonary vasoconstriction by promoting membrane depolarization, Ca(2+) influx, and contraction. Several of the K-channel subtypes identified in pulmonary artery have been implicated in the response to hypoxia, but contradictory evidence clouds the identity of the oxygen-sensing channels. Using patch-clamp techniques, this study investigated the effect of hypoxia on recombinant Kv1 channels previously identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, which has similar kinetic and pharmacological properties to native oxygen-sensitive currents. Hypoxia failed to inhibit any Kv1 channel, but it inhibited Kv3.1b channels expressed in L929 cells, as shown by a reduction of whole-cell current and single-channel activity, without affecting unitary conductance. Inhibition was retained in excised membrane patches, suggesting a membrane-delimited mechanism. Using reverse transcription-polymerase chain reaction and immunocytochemistry, Kv3.1b expression was demonstrated in PASM cells. Moreover, hypoxia inhibited a K(+) current in rabbit PASM cells in the presence of charybdotoxin and capsaicin, which preserve Kv3.1b while blocking most other Kv channels, but not in the presence of millimolar tetraethylammonium ions, which abolish Kv3.1b current. Kv3.1b channels may therefore contribute to oxygen sensing in pulmonary artery.
LanguageEnglish
Pages534-40
Number of pages7
JournalCirculation Research
Volume86
Issue number5
DOIs
Publication statusPublished - 2000

Fingerprint

Pulmonary Artery
Oxygen
Smooth Muscle Myocytes
Membranes
Charybdotoxin
Voltage-Gated Potassium Channels
Tetraethylammonium
Capsaicin
Patch-Clamp Techniques
Vasoconstriction
Reverse Transcription
Smooth Muscle
Immunohistochemistry
Hypoxia
Pharmacology
Rabbits
Polymerase Chain Reaction
Lung

Keywords

  • cell hypoxia
  • chemoreceptor cells
  • delayed rectifier potassium channels
  • gene expression
  • ion channel gating
  • Kv1.1 Potassium Channel
  • Kv1.2 Potassium Channel
  • membrane potentials
  • neuropeptides
  • oxygen
  • PC12 Cells
  • patch-clamp techniques
  • Potassium channel blockers
  • pulmonary artery
  • transfection

Cite this

Osipenko, O N ; Tate, R J ; Gurney, A M ; Tate, Rothwelle. / Potential role for kv3.1b channels as oxygen sensors. In: Circulation Research. 2000 ; Vol. 86, No. 5. pp. 534-40.
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Potential role for kv3.1b channels as oxygen sensors. / Osipenko, O N; Tate, R J; Gurney, A M; Tate, Rothwelle.

In: Circulation Research, Vol. 86, No. 5, 2000, p. 534-40.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potential role for kv3.1b channels as oxygen sensors

AU - Osipenko, O N

AU - Tate, R J

AU - Gurney, A M

AU - Tate, Rothwelle

PY - 2000

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N2 - Hypoxia inhibits voltage-gated K channels in pulmonary artery smooth muscle (PASM). This is thought to contribute to hypoxic pulmonary vasoconstriction by promoting membrane depolarization, Ca(2+) influx, and contraction. Several of the K-channel subtypes identified in pulmonary artery have been implicated in the response to hypoxia, but contradictory evidence clouds the identity of the oxygen-sensing channels. Using patch-clamp techniques, this study investigated the effect of hypoxia on recombinant Kv1 channels previously identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, which has similar kinetic and pharmacological properties to native oxygen-sensitive currents. Hypoxia failed to inhibit any Kv1 channel, but it inhibited Kv3.1b channels expressed in L929 cells, as shown by a reduction of whole-cell current and single-channel activity, without affecting unitary conductance. Inhibition was retained in excised membrane patches, suggesting a membrane-delimited mechanism. Using reverse transcription-polymerase chain reaction and immunocytochemistry, Kv3.1b expression was demonstrated in PASM cells. Moreover, hypoxia inhibited a K(+) current in rabbit PASM cells in the presence of charybdotoxin and capsaicin, which preserve Kv3.1b while blocking most other Kv channels, but not in the presence of millimolar tetraethylammonium ions, which abolish Kv3.1b current. Kv3.1b channels may therefore contribute to oxygen sensing in pulmonary artery.

AB - Hypoxia inhibits voltage-gated K channels in pulmonary artery smooth muscle (PASM). This is thought to contribute to hypoxic pulmonary vasoconstriction by promoting membrane depolarization, Ca(2+) influx, and contraction. Several of the K-channel subtypes identified in pulmonary artery have been implicated in the response to hypoxia, but contradictory evidence clouds the identity of the oxygen-sensing channels. Using patch-clamp techniques, this study investigated the effect of hypoxia on recombinant Kv1 channels previously identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, which has similar kinetic and pharmacological properties to native oxygen-sensitive currents. Hypoxia failed to inhibit any Kv1 channel, but it inhibited Kv3.1b channels expressed in L929 cells, as shown by a reduction of whole-cell current and single-channel activity, without affecting unitary conductance. Inhibition was retained in excised membrane patches, suggesting a membrane-delimited mechanism. Using reverse transcription-polymerase chain reaction and immunocytochemistry, Kv3.1b expression was demonstrated in PASM cells. Moreover, hypoxia inhibited a K(+) current in rabbit PASM cells in the presence of charybdotoxin and capsaicin, which preserve Kv3.1b while blocking most other Kv channels, but not in the presence of millimolar tetraethylammonium ions, which abolish Kv3.1b current. Kv3.1b channels may therefore contribute to oxygen sensing in pulmonary artery.

KW - cell hypoxia

KW - chemoreceptor cells

KW - delayed rectifier potassium channels

KW - gene expression

KW - ion channel gating

KW - Kv1.1 Potassium Channel

KW - Kv1.2 Potassium Channel

KW - membrane potentials

KW - neuropeptides

KW - oxygen

KW - PC12 Cells

KW - patch-clamp techniques

KW - Potassium channel blockers

KW - pulmonary artery

KW - transfection

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DO - 10.1161/​01.RES.86.5.534

M3 - Article

VL - 86

SP - 534

EP - 540

JO - Circulation Research

T2 - Circulation Research

JF - Circulation Research

SN - 0009-7330

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ER -