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.