Human T cells in silico: Modelling dynamic intracellular calcium and its influence on cellular electrophysiology.
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.
['Eichinger|Paul|P|', 'Herrmann|Alexander M|AM|', 'Ruck|Tobias|T|', 'Herty|Michael|M|', 'Gola|Lukas|L|', 'Kovac|Stjepana|S|', 'Budde|Thomas|T|', 'Meuth|Sven G|SG|', 'Hundehege|Petra|P|']
D002118:Calcium D020013:Calcium Signaling D055724:Electrophysiological Phenomena D006801:Humans D051660:Intermediate-Conductance Calcium-Activated Potassium Channels D018448:Models, Immunological D024683:Potassium Channels, Tandem Pore Domain D013601:T-Lymphocytes
Ion channels Calcium dynamics Immune system Inflammation T cell simulation