期刊
JOURNAL OF IMMUNOLOGICAL METHODS
卷 461, 期 -, 页码 78-84出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jim.2018.06.020
关键词
Immune system; Ion channels; Calcium dynamics; T cell simulation; Inflammation
资金
- German Research Foundation (DFG) [EH 469/1-1, ME 3283/6-1]
- cluster of excellence 'cells in motion - CiM'
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 (K(V)1.3, K(Ca)3.1, K-2P 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 (K(Ca)3.1) and two-pore-domain potassium (K-2P) channels.
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