Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels.
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.
Chemin
Jean
J
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS - UMR 6097, Institut Paul Hamel, 660, Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Girard
Christophe
C
Duprat
Fabrice
F
Lesage
Florian
F
Romey
Georges
G
Lazdunski
Michel
M
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000502:physiology; D027682:Cation Transport Proteins / Q000737:chemistry / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D002522:Chlorocebus aethiops; D007700:Kinetics; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology; D014162:Transfection
D027682:Cation Transport Proteins; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C085258:TRK2 protein, S cerevisiae; C104077:metabotropic glutamate receptor type 1; C068664:TRK1 protein, S cerevisiae; C420132:potassium channel subfamily K member 3; D002118:Calcium