Elementary events of InsP(3)-induced Ca2+ liberation in Xenopus oocytes: Hot spots, puffs and blips

Liberation of sequestered Ca2+ ions in Xenopus oocytes by the second messenger inositol 1,4,5-trisphosphate (InsP(3)) occurs from functionally discrete sites, which are spaced at intervals of several mu m and probably represent clusterings of InsP(3) receptor/channels (InsP(3)R) in the endoplasmic reticulum. As well as requiring InsP(3), opening of release channels is regulated by dual positive and negative feedback by cytosolic Ca2+, leading to regenerative Ca2+ transients. Because the sensitivity of this process is determined by [InsP(3)], the ability of Ca2+ ions diffusing from one location to activate increasingly distant InsP(3)R is enhanced by increasing [InsP(3)]. Together with the spatial distribution of receptors, this results in generation of a hierarchy of Ca2+ release events, which may involve individual InsP(3)R (Ca2+ 'blips'), concerted activation of several receptors within a single release site (Ca2+ 'puffs'), and recruitment of successive sites by Ca2+ diffusing over mu m distances to produce propagating Ca2+ waves. Thus, Ca2+ signalling in the oocyte is organized as at least two sizes of elemental 'building blocks'; highly localized Ca2+ transients that arise autonomously and stochastically from discrete sites at low [InsP(3)], but which become coordinated at higher [InsP(3)] to produce global Ca2+ responses.