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Open Access Research

Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety

Kun Xia1, Hui Xiong2, Yeonsook Shin2, Danling Wang12, Tom Deerinck34, Hiroto Takahashi2, Mark H Ellisman34, Stuart A Lipton23, Gang Tong23, Giannina Descalzi5, Dongxian Zhang2, Min Zhuo56* and Zhuohua Zhang12*

Author Affiliations

1 State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China

2 Burnham Institute for Medical Research, La Jolla, CA 92037, USA

3 Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA

4 National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA

5 Department of Physiology, University of Toronto, Toronto, ON., M5 S 1A8 Canada

6 Department of Brain and Cognitive Sciences, Seoul National University, Seoul 151-746, Korea

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Molecular Brain 2010, 3:23  doi:10.1186/1756-6606-3-23

Published: 2 August 2010

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.