Quantal release of Ca2+ from intracellular stores by InsP3: tests of the concept of control of Ca2+ release by intraluminal Ca2+.
A possible mechanism for the generation of 'quantal' release of intracellular Ca2+ by InsP3 (Muallem et al., J. biol. Chem. 264, 205-212 (1989)) has been put forward in which intraluminal Ca2+ levels modulate InsP3 receptor structure (Irvine, FEBS Lett. 263, 5-9 (1990)). Here we have modelled such a steady-state mechanism, with an InsP3-sensitive store plus an InsP3-insensitive one, to test its ability to mimic published data. We have also performed experiments on InsP3-stimulated rat liver microsomes to test whether the model is consistent with one-way Ca2+ fluxes at a steady state. The model can simulate quantal release, in that InsP3 produces a release of part of the stored Ca2+ which is initially rapid relative to the one-way flux. In the original form of the model, in which InsP3-modulated Ca2+ binding to the intraluminal site opens the Ca2+ channel, the range of InsP3 concentrations needed to release Ca2+ is greater than that observed. When the model is changed so that Ca2(+)-modulated InsP3 binding opens the channels, the effective InsP3 range is shortened, but the quantal release effect is reduced. Other published data on one-way fluxes, and our own data on microsomes, can be simulated when leakage from the InsP3-insensitive store is adjusted to fit the observations; these data therefore do not test the existence of a steady state in the InsP3-sensitive store. We conclude that sensitivity of Ca2+ release to intraluminal Ca2+ provides a steady-state explanation of most, but not all, current quantal release observations.(ABSTRACT TRUNCATED AT 250 WORDS)
AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
R T
RT
Tregear
A P
AP
Dawson
R F
RF
Irvine
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D051381:Rats
D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium