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, 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.