Analysis of Toxin-Induced Changes in Action Potential Shape for Drug Development

    Authors

    N. Akanda; P. Molnar; M. Stancescu;J. J. Hickman

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    J. Biomol. Screen

    Keywords

    high throughput; toxicity; cell models; electrophysiology; mechanisms; VOLTAGE-DEPENDENT CURRENTS; SODIUM-CHANNELS; NG108-15 CELLS; VERATRIDINE; DIFFERENTIATION; EXCITABILITY; BIOSENSORS; QUINIDINE; MEMBRANE; CHLORIDE; Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical

    Abstract

    The generation of an action potential (AP) is a complex process in excitable cells that involves the temporal opening and closing of several voltage-dependent ion channels within the cell membrane. The shape of an AP can carry information concerning the state of the involved ion channels as well as their relationship to cellular processes. Alteration of these ion channels by the administration of toxins, drugs, and biochemicals can change the AP's shape in a specific way, which can be characteristic for a given compound. Thus, AP shape analysis could be a valuable tool for toxin classification and the measurement of drug effects based on their mechanism of action. In an effort to begin classifying the effect of toxins on the shape of intracellularly recorded APs, patch-clamp experiments were performed on NG108-15 hybrid cells in the presence of veratridine, tetraethylammonium, and quinine. To analyze the effect, the authors generated a computer model of the AP mechanism to determine to what extent each ion channel was affected during compound administration based on the changes in the model parameters. This work is a first step toward establishing a new assay system for toxin detection and identification by AP shape analysis. (Journal of Biomolecular Screening 2009:1228-1235)

    Journal Title

    Journal of Biomolecular Screening

    Volume

    14

    Issue/Number

    10

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    1228

    Last Page

    1235

    WOS Identifier

    WOS:000272632600008

    ISSN

    1087-0571

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