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Title: TOXI-SIM-A simulation tool for the analysis of mitochondrial and plasma membrane potentials
Authors: Huber, Heinrich
Plchut, Martin
Weisová, Petronela
Düssmann, Heiko
Wenus, Jakub
Rehm, Markus
Ward, Manus W
Prehn, Jochen H M # ×
Issue Date: Jan-2009
Publisher: Elsevier/North-Holland
Series Title: Journal of Neuroscience Methods vol:176 issue:2 pages:270-275
Article number: 10.1016/j.jneumeth.2008.09.003
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 (Deltapsi(m)) over time during glutamate excitotoxicity. However, fluorescently charged dyes such as TMRM respond to changes in both Deltapsi(m) and the plasma membrane (Deltapsi(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 Deltapsi(m) and Deltapsi(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).
URI: 
ISSN: 0165-0270
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cardiovascular Sciences - miscellaneous
× corresponding author
# (joint) last author

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