The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1

TASK-1 encodes an acid- and anaesthetic-sensitive background K+ current, wh ich sets the resting membrane potential of both cerebellar granule neurons and somatic motoneurons. We demonstrate that TASK-1, unlike the other two p ore (2P) domain K+ channels, is directly blocked by submicromolar concentra tions of the endocannabinoid anandamide, independently of the CB1 and CB2 r eceptors, In cerebellar granule neurons, anandamide also blocks the TASK-1 standing-outward K+ current, IKso, and induces depolarization. Anandamide-i nduced neurobehavioural effects are only partly reversed by antagonists of the cannabinoid receptors, suggesting the involvement of alternative pathwa ys. TASK-1 constitutes a novel sensitive molecular target for this endocann abinoid.