Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels

EMBO J. 2003 Oct 15;22(20):5403-11. doi: 10.1093/emboj/cdg528.


Group I metabotropic glutamate receptors (mGluRs) are implicated in diverse processes such as learning, memory, epilepsy, pain and neuronal death. By inhibiting background K(+) channels, group I mGluRs mediate slow and long-lasting excitation. The main neuronal representatives of this K(+) channel family (K(2P) or KCNK) are TASK and TREK. Here, we show that in cerebellar granule cells and in heterologous expression systems, activation of group I mGluRs inhibits TASK and TREK channels. D-myo-inositol-1,4,5-triphosphate and phosphatidyl-4,5-inositol-biphosphate depletion are involved in TASK channel inhibition, whereas diacylglycerols and phosphatidic acids directly inhibit TREK channels. Mechanisms described here with group I mGluRs will also probably stand for many other receptors of hormones and neurotransmitters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • COS Cells
  • Calcium / physiology
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / physiology
  • Cells, Cultured
  • Cerebellum / physiology*
  • Chlorocebus aethiops
  • Kinetics
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / physiology
  • Neurons / physiology*
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Tandem Pore Domain*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / physiology*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / physiology
  • Transfection


  • Cation Transport Proteins
  • Kcnk9 protein, rat
  • Nerve Tissue Proteins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Receptors, Metabotropic Glutamate
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • TRK2 protein, S cerevisiae
  • metabotropic glutamate receptor type 1
  • TRK1 protein, S cerevisiae
  • potassium channel subfamily K member 3
  • Calcium