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.
