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

Inositol (1,4,5)-trisphosphate (IP3) liberates intracellular Ca2+ both as localized 'puffs' and as repetitive waves that encode information in a frequency-dependent manner. Using video-rate confocal imaging, together with photorelease of IP3 in Xenopus oocytes, we investigated the roles of puffs in determining the periodicity of global Ca2+ waves. Wave frequency is not delimited solely by cyclical recovery of the cell's ability to support wave propagation, 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 apposition to neighboring puff sites, preferentially entrain both the temporal frequency and spatial directionality of Ca2+ waves. Although summation of activity from many stochastic puff sites promotes the generation of regularly periodic global Ca2+ signals, the properties of individual Ca2+ puffs control the kinetics of Ca2+ spiking and the (higher) frequency of subcellular spikes in their local microdomain.