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Transmitter regulation of voltage-dependent K+ channels expressed in Xenopus oocytes

M P Kavanaugh1, M J Christie, P B Osborne

  • 1Vollum Institute, Oregon Health Sciences University, Portland 97201.

The Biochemical Journal
|August 1, 1991
PubMed

Insights

Voltage-dependent potassium channels were inhibited by serotonin (5-HT) in Xenopus oocytes. This inhibition was mediated by inositol trisphosphate, not calcium, suggesting a novel signaling pathway for 5-HT2 receptors.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Cell Physiology

Background:

  • Voltage-dependent potassium channels (Kv channels) play crucial roles in neuronal excitability and cellular signaling.
  • Serotonin (5-HT) receptors, particularly the 5-HT2 family, are implicated in various physiological and pathological processes.
  • The interaction between Kv channels and G protein-coupled receptors like 5-HT2 receptors is complex and involves intracellular signaling cascades.

Purpose of the Study:

  • To investigate the functional interaction between specific voltage-dependent potassium channels (RBK1, RBK2, RGK5) and 5-hydroxytryptamine (5-HT2) receptors.
  • To elucidate the intracellular signaling mechanisms by which 5-HT modulates Kv channel activity.
  • To determine the role of calcium and inositol trisphosphate in 5-HT-mediated inhibition of Kv currents.

Main Methods:

  • Co-expression of voltage-dependent K+ channel subunits (RBK1, RBK2, RGK5) and 5-HT2 receptors in Xenopus oocytes.
  • Two-electrode voltage clamp recordings to measure K+ currents.
  • Application of 5-HT and intracellular injection of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3).
  • Analysis of K+ currents in excised membrane patches with varying intracellular Ca2+ concentrations.

Main Results:

  • Co-expression of Kv channels and 5-HT2 receptors resulted in functional K+ currents.
  • Application of 5-HT (100 nM-10 microM) inhibited K+ currents by up to 90%.
  • Intracellular injection of Ins(1,4,5)P3 mimicked the inhibitory effect of 5-HT.
  • Increasing intracellular Ca2+ concentration in excised patches did not decrease K+ current, suggesting Ca2+ is not the primary mediator.

Conclusions:

  • 5-HT, acting through 5-HT2 receptors, significantly inhibits voltage-dependent K+ channel activity (RBK1, RBK2, RGK5) in Xenopus oocytes.
  • The inhibitory effect is mediated by inositol 1,4,5-trisphosphate, indicating a specific intracellular signaling pathway.
  • Calcium ions do not appear to play a direct role in the 5-HT-induced inhibition of these Kv channels.

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