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

J Immunol Methods. 2018 Oct:461:78-84. doi: 10.1016/j.jim.2018.06.020. Epub 2018 Jul 3.

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.

Keywords: Calcium dynamics; Immune system; Inflammation; Ion channels; T cell simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / immunology
  • Calcium Signaling / immunology*
  • Electrophysiological Phenomena / immunology*
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels / immunology*
  • Models, Immunological*
  • Potassium Channels, Tandem Pore Domain / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human
  • Potassium Channels, Tandem Pore Domain
  • Calcium