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Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety |
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| Authors: | Kun Xia Hui Xiong Yeonsook Shin Danling Wang Tom Deerinck Hiroto Takahashi Mark H Ellisman Stuart A Lipton Gang Tong Giannina Descalzi Dongxian Zhang Min Zhuo Zhuohua Zhang |
| Institution: | 1. State Key Laboratory of Medical Genetics, Central South University, 410078, Changsha, Hunan, China 2. Burnham Institute for Medical Research, 92037, La Jolla, CA, USA 3. Department of Neurosciences, University of California, San Diego, 92093, La Jolla, CA, USA 4. National Center for Microscopy and Imaging Research, University of California, San Diego, 92093, La Jolla, CA, USA 5. Department of Physiology, University of Toronto, M5 S 1A8, Toronto, Canada 6. Department of Brain and Cognitive Sciences, Seoul National University, 151-746, Seoul, Korea |
| 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. |
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