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.
Highlights
Neuronal calcium sensor (NCS) proteins contain EFhand calcium binding domains and are conserved throughout evolution [1,2,3]
Overexpression of K+ channel interacting protein 1 (KChIP1) facilitates GABA-mediated synaptic transmission in cultured hippocampal neurons We investigated the role of KChIP1 in modulating inhibitory synaptic transmission in cultured hippocampal neurons infected with recombinant Semliki Forest viral (SFV) particles encoding either a KChIP1-EGFP fusion protein or EGFP protein alone
KChIP1 KO mice display enhanced anxiety-like behavior Given our observations that KChIP1 potentiates presynaptic GABA release and that benzodiazepines, commonly used for the relief of anxiety, are thought to act by enhancing the action of the inhibitory transmitter GABA, we investigated the possible role of KChIP1 in anxiety-like behavior and compared KChIP1 KO and WT mice in a battery of anxiety related tasks
Summary
Neuronal calcium sensor (NCS) proteins contain EFhand calcium binding domains and are conserved throughout evolution [1,2,3]. In humans, they are encoded by 14 genes, some of which alternatively splice during transcription. Based on the order of their evolutionary appearance, NCS proteins are classified into class A to E5 subfamilies [1,4]. Four KChIP proteins constitute the fifth subfamily (Class E) and are unique to mammals. KChIPs interact with voltagegated potassium channels and presenilins [5,6,7,8]. KChIP1, KChIP3, KChIP4 are expressed predominantly in brain, while KChIP2 is highly expressed in both heart and brain [7,9]
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