Incorporating Ryanodine Receptor Calcium Release Channels into a Computational Model of Calcium Concentration in T-Lymphocytes

Abstract

The vital process of intracellular calcium (Ca 2+ ) signaling in T-lymphocytes control complex immune responses, and disruptions can cause autoimmune and inflammatory disorders. The activation of T-cells is fine-tuned by various pathways interacting with membrane potential, messengers, and other enzymes that eventually trigger intracellular calcium release. In cardiac and skeletal muscle, ryanodine receptors (RyR) are crucial to the release of calcium, facilitating contractions and relaxations of striated muscle cells. However, RyR also plays an important role in human T-cell activation, regulating calcium release in activated T-cells through bidirectional coupling of calcium release-activated calcium (CRAC) channels. The mechanism of RyR has been demonstrated in vitro, but it is important to explore this system quantitatively to describe various interactions and modulations in the T-cell. We modified an existing T-cell model simulating the activation of CRAC channels with intracellular components, adding RyR1, RyR2, and RyR3 isoforms. Our model simulated the role of RyR in an activated and resting T-cell, potentially providing a tool to modulate immune responses in humans.