Application of acetylcholine to Xenopus oocytes evoked increases in th
e cytosolic free calcium ion concentration ([Ca2+](i)) after latencies
of up to several seconds depending on the agonist dose. Higher acetyl
choline concentrations evoked responses with larger amplitudes and sho
rter latencies. The latencies of responses to acetylcholine could be i
ncreased by application of caffeine, injection of calcium buffers or d
epletion of intracellular calcium stores. Acute inhibition of endoplas
mic reticulum calcium pumps without substantial reduction of the calci
um store content (by application of thapsigargin shortly before agonis
t stimulation) reduced the latencies of responses to acetylcholine. A
schematic and mathematical model are presented to show a possible mech
anism by which a calcium signal is initiated following a latent period
after the elevation of the inositol trisphosphate concentration. Duri
ng the latent period, calcium is slowly released from the intracellula
r stores. The released calcium is rapidly buffered by cytosolic calciu
m-binding proteins and some is resequestered into the stores by calciu
m pumps. The [Ca2+](i) changes very little until the buffering is loca
lly saturated. The [Ca2+](i) then rises above a threshold concentratio
n which evokes an explosive release of calcium due to positive feedbac
k by calcium on the inositol trisphosphate receptor.