Role of elementary Ca2+ puffs in generating repetitive Ca2+ oscillations

Inositol (1,4,5)-trisphosphate (IP3) liberates intracellular Ca2+ both as l ocalized 'puffs' and as repetitive waves that encode information in a frequ ency-dependent manner. Using video-rate confocal imaging, together with pho torelease of IP3 in Xenopus oocytes, we investigated the roles of puffs in determining the periodicity of global Ca2+ waves. Wave frequency is not del imited solely by cyclical recovery of the cell's ability to support wave pr opagation, but further involves sensitization of Ca2+-induced Ca2+ release by progressive increases in puff frequency and amplitude at numerous sites during the interwave period, and accumulation of pacemaker Ca2+, allowing a puff at a 'focal' site to trigger a subsequent wave. These specific 'focal ' sites, distinguished by their higher sensitivity to IP3 and close apposit ion to neighboring puff sites, preferentially entrain both the temporal fre quency and spatial directionality of Ca2+ waves. Although summation of acti vity from many stochastic puff sites promotes the generation of regularly p eriodic global Ca2+ signals, the properties of individual Ca2+ puffs contro l the kinetics of Ca2+ spiking and the (higher) frequency of subcellular sp ikes in their local microdomain.