N. Callamaras et I. Parker, Phasic characteristic of elementary Ca2+ release sites underlies quantal responses to IP3, EMBO J, 19(14), 2000, pp. 3608-3617
Ca2+ liberation by inositol 1,4,5-trisphosphate (IP3) is 'quantal', in that
low [IP3] causes only partial Ca2+ release, but further increasing [IP3] e
vokes more release. This characteristic allows cells to generate graded Ca2
+ signals, but is unexpected, given the regenerative nature of Ca2+-induced
Ca2+ release through IP3 receptors. Two models have been proposed to resol
ve this paradox: (i) all-or-none Ca2+ release from heterogeneous stores tha
t empty at varying [IP3]; and (ii) phasic liberation from homogeneously sen
sitive stores. To discriminate between these hypotheses, we imaged subcellu
lar Ca2+ puffs evoked by IP3 in Xenopus oocytes where release sites were fu
nctionally uncoupled using EGTA. Puffs were little changed by 300 mu M intr
acellular EGTA, but sites operated autonomously and did not propagate waves
. Photoreleased IP3 generated flurries of puffs-different to the prolonged
Ca2+ elevation following waves in control cells-and individual sites respon
ded repeatedly to successive increments of [IP3]. These data support the se
cond hypothesis while refuting the first, and suggest that local Ca2+ signa
ls exhibit rapid adaptation, different to the slower inhibition following g
lobal Ca2+ waves.