Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2

摘要: G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of protein-coupled receptors for neurotransmitters and hormones may play an important role in the regulation neuronal excitability. GIRK be neurodevelopment, as suggested by recent finding that a point mutation pore region GIRK2 (G156S) is responsible weaver (wv) phenotype. The G156S gene gives rise to exhibit loss selectivity also exert dominant-negative effects on Gβγ-activated currents. To investigate physiological GIRK2, we generated mutant mice lacking GIRK2. Unlike wv/wv mice, −/− morphologically indistinguishable from wild-type suggesting wv phenotype likely due abnormal function. Like have much reduced GIRK1 expression brain. They develop spontaneous seizures more susceptible pharmacologically induced using γ-aminobutyric acid antagonist. Moreover, wv/− milder cerebellar abnormalities than indicating dosage effect mutation. Our results indicate phenotypes arise gain-of-function mediators excitability vivo.