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Author(s):Huang, Zhuoli
Contributor(s):Chung, Hee Jung
Subject(s):homeostatic intrinsic plasticity
Kv7 channels
Abstract:Intrinsic excitability regulation ensures neurons fire within an optimal operating range; its dysfunction is hypothesized to cause multiple neuronal hyperexcitability disorders including epilepsy and chronic pain. However, the molecular players and the sites of this excitability modulation remain largely unknown. We have recently reported that chronic activity blockade by voltage-gated sodium (Nav) channel antagonist tetrodotoxin (TTX) leads to the homeostatic scaling of action potential firing rates in hippocampal culture neurons and identified Kv7 potassium channel genes and current as possible key players of this regulation. Kv7 channels composed of Kv7.2 and Kv7.3 subunits are voltage-gated potassium channels that potently limits repetitive and burst firings of action potentials in neurons. Consistent with their ability to inhibit excitability, they are preferentially enriched at the plasma membrane of the axon with the highest concentration at the axon initial segment (AIS). In this study, I investigated the extent to which chronic activity blockade alters expression of Kv7 channels, and their interacting proteins including calmodulin (CaM), Ankyrin-G, AKAP79/150, and syntaxin-1A as well as the upstream events of expression regulation of these proteins. Immunofluorescence microscopy revealed a noticeable decrease in Kv7.2 expression at the axonal initial segments (AIS) of hippocampal neurons upon 48 h TTX treatment, whereas the same treatment increased the level of AIS marker Ankyrin-G and shortened the distance from soma to the start of the AIS. Bioinformatics analysis implies some transcription factors that may be important in these regulations. Further investigation of chronic inactivity-induced changes of CaM, AKAP79/150, and syntaxin 1A in the axon is needed. These results suggest that alterations of Kv7 channel protein complex at the AIS may in part contribute to the expression of homeostatic intrinsic plasticity.
Issue Date:2017
Genre:Dissertation / Thesis
Sponsor:a RO1 NS083402 grant from the National Institute of Health, National Institute of Neurological Disorders and Stroke (Hee Jung Chung); the ICR start-up fund from the University of Illinois at Urbana-Champaign (Hee Jung Chung); the James Scholar Preble Research Award from Biochemistry Department, the University of Illinois at Urbana- Champaign (Zhuoli Huang); and a Research Support Grant from the Office of Undergraduate Research, the University of Illinois at Urbana-Champaign (Zhuoli Huang)
Rights Information:Copyright 2017 Zhuoli Huang
Date Available in IDEALS:2017-05-15

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