Human T cells in silico: Modelling their electrophysiological behaviour in health and disease.
Although various types of ion channels are known to have an impact on human T cell effector functions, their exact mechanisms of influence are still poorly understood. The patch clamp technique is a well-established method for the investigation of ion channels in neurons and T cells. However, small cell sizes and limited selectivity of pharmacological blockers restrict the value of this experimental approach. Building a realistic T cell computer model therefore can help to overcome these kinds of limitations as well as reduce the overall experimental effort. The computer model introduced here was fed off ion channel parameters from literature and new experimental data. It is capable of simulating the electrophysiological behaviour of resting and activated human CD4(+) T cells under basal conditions and during extracellular acidification. The latter allows for the very first time to assess the electrophysiological consequences of tissue acidosis accompanying most forms of inflammation.
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany. Electronic address: petra.ehling@uni-muenster.de.
Petra
P
Ehling
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany.
Patrick
P
Meuth
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany; Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München TUM, Ismaninger Strasse 22, 81675 Munich, Germany.
Paul
P
Eichinger
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany.
Alexander M
AM
Herrmann
Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Stefan
S
Bittner
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany; Wellcome Trust and MRC Cambridge Stem Cell Institute, and Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge, UK.
Matthias
M
Pawlowski
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany.
Susann
S
Pankratz
RWTH Aachen University, Mathematics (Continuous optimization), Templergraben 55, 52056 Aachen, Germany.
Michael
M
Herty
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Robert-Koch-Str. 27a, 48149 Münster, Germany.
Thomas
T
Budde
Department of Neurology, and Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany.
Sven G
SG
Meuth
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002412:Cations; D003198:Computer Simulation; D004194:Disease; D055724:Electrophysiological Phenomena; D006262:Health; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*
D002412:Cations; D007473:Ion Channels; D011188:Potassium; D002118:Calcium
Immune system; Inflammation; Ion channels; Patch clamp recordings; T cell simulation; Tissue acidosis