Inositol (1,4,5)-trisphosphate (IP3) evokes Ca2+ liberation in Xenopus oocy
tes as elementary events (Ca2+ puffs) that become coupled to propagate Ca2 waves with increasing [IP3], To investigate this transition between local
and global Ca2+ signaling, we developed an optical method for evoking rapid
subcellular Ca2+ elevations, while independently photoreleasing IP3 and si
multaneously recording confocal Ca2+ images. Focal Ca2+ elevations triggere
d waves within 100 ms of photoreleasing IP3, compared with latencies of sec
onds following photorelease of IP3 alone. Wave velocity varied with [IP3] b
ut was independent of time after photorelease of IP3, indicating that delay
ed wave initiation did not involve slow binding of IP3 to its receptors, Th
e amount of Ca2+ required to trigger a wave was similar to 10-fold greater
than the average size of puffs, and puffs showed no progressive increase in
magnitude before waves initiated. Instead, Ca2+ puffs contributed to a slo
w rise in basal free [Ca2+], which further increased puff frequency and sen
sitized IP3 receptors so that individual events then triggered waves. Becau
se the wale threshold is much greater than the size of the elementary puff,
cells can employ both local and global signaling mechanisms, and the summa
tion of stochastic behavior of elementary events allows generation of repro
ducible periodic waves.