Potential role for kv3.1b channels as oxygen sensors

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

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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.
Original languageEnglish
Pages (from-to)534-40
Number of pages7
JournalCirculation Research
Volume86
Issue number5
DOIs
Publication statusPublished - 2000

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

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