TOXI-SIM-A simulation tool for the analysis of mitochondrial and plasma membrane potentials

Heinrich J. Huber, Martin Plchut, Petronela Weisová, Heiko Düssmann, Jakub Wenus, Markus Rehm, Manus Ward, Jochen H.M. Prehn*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    Changes in the electrochemical gradients across biological membranes are excellent indicators of pathophysiological processes, drug action, or drug toxicity. Our previous studies have utilized the potentiometric probe tetramethylrhodamine methyl ester (TMRM) to characterize changes in mitochondrial function by monitoring alterations in the mitochondrial membrane potential (Δψ m ) over time during glutamate excitotoxicity. However, fluorescently charged dyes such as TMRM respond to changes in both Δψ m and the plasma membrane (Δψ p ) potentials making whole cell fluorescence data difficult to interpret. Here we have implemented a mathematical model that exploits the Nernstian behaviour of TMRM and uses automated Newton based root-finding fitting (TOXI-SIM) to model changes in TMRM fluorescence from multiple cells simultaneously, providing output on changes in Δψ m and Δψ p over time. Based on Ca 2+ responses, TOXI-SIM allows for an accurate modelling of TMRM traces for different injury paradigms (necrosis, apoptosis, tolerance). TOXI-SIM is provided as a user friendly public web service for trace analysis, with an additional online data base provided for the storage and retrieval of experimental traces (http://systemsbiology.rcsi.ie/tmrm/index.html).

    Original languageEnglish (US)
    Pages (from-to)270-275
    Number of pages6
    JournalJournal of Neuroscience Methods
    Volume176
    Issue number2
    DOIs
    StatePublished - Jan 30 2009

    Keywords

    • Bioenergetics
    • Excitotoxicity
    • Glutamate
    • Mathematical modelling
    • Mitochondrial membrane potential
    • Plasma membrane potential

    ASJC Scopus subject areas

    • Neuroscience(all)

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