Elementary Events of InsP3-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 (InP3) occurs from functionally discrete sites, which are spaced at intervals of several microns and probably represent clusterings of InsP3 receptor/channels (InsP3R) in the endoplasmic reticulum. As well as requiring InsP3, 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 [InsP3], the ability of Ca2+ ions diffusing from one location to activate increasingly distant InsP3R is enhanced by increasing [InsP3]. Together with the spatial distribution of receptors, this results in generation of a hierarchy of Ca2+ release events, which may involve individual InsP3R (Ca2+ 'blips'), concerted activation of several receptors within a single release site (Ca2+ 'puffs'), and recruitment of successive sites by Ca2+ diffusing over micron 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 [InsP3], but which become coordinated at higher [InsP3] to produce global Ca2+ responses.