BRADFORD SCHOLARS

    • Sign in
    View Item 
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Bradford ScholarsCommunitiesAuthorsTitlesSubjectsPublication DateThis CollectionAuthorsTitlesSubjectsPublication Date

    My Account

    Sign in

    HELP

    Bradford Scholars FAQsCopyright Fact SheetPolicies Fact SheetDeposit Terms and ConditionsDigital Preservation Policy

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Validation of a voltage-sensitive dye (di-4-ANEPPS)-based method for assessing drug-induced delayed repolarisation in Beagle dog left ventricular midmyocardial myocytes

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Publication date
    2009
    Author
    Hardy, Matthew E.
    Pollard, C.E.
    Small, B.G.
    Bridgland-Taylor, M.
    Woods, A.J.
    Valentin, J.-P.
    Abi-Gerges, N.
    Keyword
    Action potential duration
    Cardiac ion channels
    Dog species
    IonWorks (TM)
    Left ventricular midmyocardial myocytes
    Methods
    Voltage-sensitive dye
    Peer-Reviewed
    yes
    
    Metadata
    Show full item record
    Abstract
    Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay could be used instead. Methods Optical APs were recorded using di-4-ANEPPS in electrically field stimulated Beagle left ventricular midmyocardial myocytes (LVMMs). Pharmacological properties of di-4-ANEPPS on the main cardiac ion channels that shape the ventricular AP were investigated using IonWorks™ and conventional electrophysiology. Effects of 9 reference drugs (dofetilide, E4031, d-sotalol, ATXII, cisapride, terfenadine, alfuzosin, diltiazem and pinacidil) with known APD-modulating effects were assessed on optically measured APD at 1 Hz. Results Under optimum conditions, 0.1 μM di-4-ANEPPS could be used to monitor APs paced at 1 Hz during nine, 5 s exposures without altering APD. di-4-ANEPPS had no effect on either hIERG, hINa, hIKs and hIto currents in transfected CHO cells (up to 10 µM) or ICa,L current in LVMMs (at 16 µM). di-4-ANEPPS had no effect on APs recorded with microelectrodes at 1 or 0.5 Hz over a period of 30 min di-4-ANEPPS displayed the sensitivity to record changes in optically measured APD in response to altered pacing frequencies and sequential vehicle additions did not affect the optically measured APD. APD data obtained with 9 reference drugs were as expected except (i) d-sotalol-induced increases in duration were smaller than those caused by other IKr blockers and (ii) increases in APD were not detected using low concentrations of terfenadine. Discussion Early in drug discovery, the di-4-ANEPPS-based method can reliably be used to assess drug effects on APD as part of a cardiac risk assessment strategy.
    URI
    http://hdl.handle.net/10454/16509
    Version
    No full-text in the repository
    Citation
    Hardy ME, Pollard CE, Small BG, Bridgland-Taylor M, Harmer AR, Woods AJ, Valentin J-P and Abi-Gerges N (2009) Validation of a voltage-sensitive dye (di-4-ANEPPS)-based method for assessing drug-induced delayed repolarisation in Beagle dog left ventricular midmyocardial myocytes. Journal of Pharmacological and Toxicological Methods. Focused Issue on Methods in Safety Pharmacology. 60: 94-106.
    Link to publisher’s version
    https://doi.org/10.1016/j.vascn.2009.03.005
    Type
    Article
    Collections
    Life Sciences Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    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.