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The endocannabinoid anandamide is a direct and selective blocker of the background K + channel TASK‐1
Author(s) -
Maingret François,
Patel Amanda J.,
Lazdunski Michel,
Honoré Eric
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.47
Subject(s) - anandamide , endocannabinoid system , cannabinoid receptor , biology , depolarization , neuroscience , cannabinoid , biophysics , receptor , pharmacology , biochemistry , agonist
TASK‐1 encodes an acid‐ and anaesthetic‐sensitive background K + current, which sets the resting membrane potential of both cerebellar granule neurons and somatic motoneurons. We demonstrate that TASK‐1, unlike the other two pore (2P) domain K + channels, is directly blocked by submicromolar concentrations of the endocannabinoid anandamide, independently of the CB1 and CB2 receptors. In cerebellar granule neurons, anandamide also blocks the TASK‐1 standing‐outward K + current, IKso, and induces depolarization. Anandamide‐induced neurobehavioural effects are only partly reversed by antagonists of the cannabinoid receptors, suggesting the involvement of alternative pathways. TASK‐1 constitutes a novel sensitive molecular target for this endocannabinoid.