The Role of Ion Channels in Regulating Calcium Homeostasis and Immune Function

Abstract

Calcium ions (Ca2+) are important intracellular messengers that govern immune-cell activation, proliferation, differentiation, migration, cytokine release and antimicrobial action. Immune cells are tightly regulated by calcium homeostasis through the coordinated activity of ion channels, intracellular calcium storage, membrane transporters and calcium-binding proteins. Ion channels involved in the initiation, amplification and termination of calcium signals include calcium-release-activated calcium (CRAC) channels, transient receptor potential (TRP) channels, purinergic P2X receptors, potassium channels and chloride channels. Store-operated calcium entry through stromal interaction molecule 1 (STIM1) and ORAI1 is particularly crucial for T-lymphocyte activation and adaptive immunity. Calcium signalling in innate immunity cells is involved in phagocytosis, inflammasome activation, chemotaxis, oxidative burst and generation of inflammatory mediators. Disruption of ion-channel function can weaken host defence or induce pathological inflammation, autoimmune, and immunological dysfunction associated with chronic illnesses. Therefore, ion channels are rapidly being acknowledged as possible therapeutic targets for immune modulation.