• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Elucidating the Molecular Mechanisms of Gating of Human ether-a-go-go Related Gene Potassium Channels

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Gustina_umaryland_0373D_10307.pdf
    Size:
    5.223Mb
    Format:
    PDF
    Download
    Author
    Gustina, Ahleah Suzanne
    Advisor
    Trudeau, Matthew C.
    Date
    2012
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    The human ether-a-go-go related gene (hERG) potassium channel is a key component of the repolarization of the ventricular action potential and a modulator of neuronal excitability. The N-terminal regions of hERG are known to contribute to the modulation of inactivation and deactivation gating; however, the specific contributions of N-terminal domains and the mechanism of modulation have not been determined. The data presented here demonstrate a key modulatory role by an N-terminal region through interaction with an intracellular C-terminal domain. Using a genetically encoded ether-a-go-go/Per-Arnt-Sim (eag/PAS) domain fragment and FRET spectroscopy, we showed that the eag/PAS domain was the primary determinant of deactivation gating and was able to form a stable interaction with N-truncated channels and to compensate for eag/PAS domain mutations in full length channels. We hypothesized that the C-terminal cyclic nucleotide binding domain (CNBD) was a site of interaction of the eag/PAS domain. CNBD-deleted channels were shown to have abnormal deactivation gating, similar to that seen with N-terminal region-deleted channels. A protein interaction experiment showed direct binding between the eag/PAS domain and a C-linker/CNBD protein. This interaction was demonstrated to occur between adjacent subunits of the hERG channel. To further investigate the role of N-terminal domains in gating, we probed N-terminal region deleted channels with eag/PAS and proximal domain fragments, and determined that the eag/PAS domain is also a key regulator of hERG rectification and inactivation properties; whereas, the proximal domain is involved only in steady-state activation gating. Together, our data indicate that the eag/PAS domain is a key modulator of hERG gating that functions to modulate gating by a direct interaction with the CNBD.
    Description
    University of Maryland in Baltimore. Neuroscience. Ph.D. 2012
    Keyword
    CNBD
    eag domain
    hERG
    LQTS
    PAS
    Ether-A-Go-Go Potassium Channels
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1688
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.