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

Jean Chemin; Christophe Girard; Fabrice Duprat; Florian Lesage; Georges Romey; Michel Lazdunski

doi:10.1093/emboj/cdg528

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.

Authors

Jean Chemin¹, Christophe Girard, Fabrice Duprat, Florian Lesage, Georges Romey, Michel Lazdunski

Affiliation

¹ Institut de Pharmacologie Moléculaire et Cellulaire, CNRS - UMR 6097, Institut Paul Hamel, 660, Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.

Abstract

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

Substances

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