Human T cells in silico: Modelling dynamic intracellular calcium and its influence on cellular electrophysiology

Journal of Immunological Methods
Paul EichingerPetra Hundehege

Abstract

A network of ion currents influences basic cellular T cell functions. After T cell receptor activation, changes in highly regulated calcium levels play a central role in triggering effector functions and cell differentiation. A dysregulation of these processes might be involved in the pathogenesis of several diseases. We present a mathematical model based on the NEURON simulation environment that computes dynamic calcium levels in combination with the current output of diverse ion channels (KV1.3, KCa3.1, K2P channels (TASK1-3, TRESK), VRAC, TRPM7, CRAC). In line with experimental data, the simulation shows a strong increase in intracellular calcium after T cell receptor stimulation before reaching a new, elevated calcium plateau in the T cell's activated state. Deactivation of single ion channel modules, mimicking the application of channel blockers, reveals that two types of potassium channels are the main regulators of intracellular calcium level: calcium-dependent potassium (KCa3.1) and two-pore-domain potassium (K2P) channels.

Citations

Feb 29, 2020·International Journal of Molecular Sciences·Ferenc PappGyorgy Panyi
Nov 11, 2020·European Journal of Immunology·Juncal Fernández-OrthSven G Meuth
Oct 9, 2020·Journal of Immunological Methods·Alexander M HerrmannThomas Budde

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