title: Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice.
abstract: Idiopathic epilepsy is characterized by seizures without a clear etiology and is believed to have a strong genetic component but exhibits a complex inheritance pattern. Genetic factors seem to confer a low seizure threshold to susceptible individuals and thereby enhance epileptogenesis. However, the identity of susceptibility genes and the mechanisms regulating seizure threshold are still poorly understood. Here, we describe that reduced expression of RalBP1, a downstream effector of the small GTPases RalA and RalB, lowers the seizure threshold in mice. The intraperitoneal injection of the chemoconvulsant pentylenetetrazol induced more severe seizures in RalBP1 hypomorphic mice than in their wild-type littermates. The reduction of RalBP1 in the brain has no effect on neuronal excitability, but does decrease the inhibitory synaptic transmission onto CA1 pyramidal neurons. This impaired synaptic inhibition was associated with the loss of GABAergic interneurons in the CA1 subfield of the hippocampus. The present study identifies RalBP1 as a gene regulating the seizure threshold in mice and provides direct evidence for the role of RalBP1 in synaptic inhibition in vivo.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Bae
authors.forename: Woosuk
authors.initials: W
authors.lastname: Chung
authors.forename: Kihoon
authors.initials: K
authors.lastname: Han
authors.forename: Kyeong Yeol
authors.initials: KY
authors.lastname: Park
authors.forename: Hosun
authors.initials: H
authors.lastname: Kim
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000502:physiology; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity; D017966:Pyramidal Cells / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*
chemical_list: D020690:GTPase-Activating Proteins; C490620:Ralbp1 protein, mouse; D010433:Pentylenetetrazole