Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety.
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.
Xia
Kun
K
State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
Xiong
Hui
H
Shin
Yeonsook
Y
Wang
Danling
D
Deerinck
Tom
T
Takahashi
Hiroto
H
Ellisman
Mark H
MH
Lipton
Stuart A
SA
Tong
Gang
G
Descalzi
Giannina
G
Zhang
Dongxian
D
Zhuo
Min
M
Zhang
Zhuohua
Z
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*
C496754:Kcnip1 protein, mouse; D051605:Kv Channel-Interacting Proteins; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid