title: Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety.
abstract: K+ channel interacting protein 1 (KChIP1) is a neuronal calcium sensor (NCS) protein that interacts with multiple intracellular molecules. Its physiological function, however, remains largely unknown. We report that KChIP1 is predominantly expressed at GABAergic synapses of a subset of parvalbumin-positive neurons in the brain. Forced expression of KChIP1 in cultured hippocampal neurons increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs), reduced paired pulse facilitation of autaptic IPSCs, and decreases potassium current density. Furthermore, genetic ablation of KChIP1 potentiated potassium current density in neurons and caused a robust enhancement of anxiety-like behavior in mice. Our study suggests that KChIP1 is a synaptic protein that regulates behavioral anxiety by modulating inhibitory synaptic transmission, and drugs that act on KChIP1 may help to treat patients with mood disorders including anxiety.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Yeonsook
authors.initials: Y
authors.lastname: Shin
authors.forename: Danling
authors.initials: D
authors.lastname: Wang
authors.forename: Tom
authors.initials: T
authors.lastname: Deerinck
authors.forename: Hiroto
authors.initials: H
authors.lastname: Takahashi
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
authors.forename: Gang
authors.initials: G
authors.lastname: Tong
authors.forename: Giannina
authors.initials: G
authors.lastname: Descalzi
authors.forename: Dongxian
authors.initials: D
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Zhuohua
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017353:Gene Deletion; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: C496754:Kcnip1 protein, mouse; D051605:Kv Channel-Interacting Proteins; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid