Mechanisms and functions of calcium microdomains produced by ORAI channels, d-myo-inositol 1,4,5-trisphosphate receptors, or ryanodine receptors

Abstract

With the discovery of local Ca²⁺ signals in the 1990s the concept of 'elementary Ca²⁺ signals' and 'fundamental Ca²⁺ signals' was developed. While 'elementary Ca²⁺signals' relate to optical signals gained by activity of small clusters of Ca²⁺channels, 'fundamental signals' describe such optical signals that arise from opening of single Ca²⁺channels. In this review, we discuss (i) concepts of local Ca²⁺ signals and Ca²⁺ microdomains, (ii) molecular mechanisms underlying Ca²⁺ microdomains, (iii) functions of Ca²⁺ microdomains, and (iv) mathematical modelling of Ca²⁺ microdomains. We focus on Ca²⁺ microdomains produced by ORAI channels, D-myo-inositol 1,4,5-trisphosphate receptors, or ryanodine receptors. In summary, research on local Ca²⁺ signals in different cell models aims to better understand how cells use the Ca²⁺ toolkit to produce Ca²⁺ microdomains as relevant signals for specific cellular responses, but also how local Ca²⁺ signals as building blocks merge into global Ca²⁺ signaling.

Keywords: 3D mathematical modelling; Ca(2+) channels; Ca(2+) microdomains; Ca(2+) signaling; Ca(2+) toolkit; ORAI; Second messengers; d-myo-inositol 1,4,5-trisphosphate receptor; ryanodine receptor.