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

• Published in: The EMBO journal Vol. 22; no. 20; pp. 5403 - 5411
• Main Authors: Lazdunski, Michel, Chemin, Jean, Girard, Christophe, Duprat, Fabrice, Lesage, Florian, Romey, Georges
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15-10-2003; Blackwell Publishing Ltd; EMBO Press; Oxford University Press
• Subjects: Animals; Binding Sites; Calcium - physiology; Cation Transport Proteins - chemistry; Cation Transport Proteins - physiology; Cells, Cultured; Cercopithecus aethiops; Cerebellum - physiology; COS Cells; diacylglycerol; glutamate; Hormones; IP3; Kinetics; Models, Molecular; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - physiology; Neurons - physiology; phosphatidic acid; PIP2; 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
• ISSN: 0261-4189; 1460-2075; 1460-2075
• 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 (K2P 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.