Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep

[摘要] Study ObjectivesA major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes nonrapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator.

[学科分类] 生理学

[关键词] G-protein-gated inwardly rectifying potassium channels;hippocampus;hypothalamus;ML297;patch clamp recording;sleep