Feedback control of inositol trisphosphate signalling bycalcium.

Inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release depends on the cytoplasmic concentration of Ca2+ in a biphasic manner: activated with the increase in Ca2+ up to approximately 300 nM and inhibited by its further increase. Kinetic studies of the Ca2+ release with rapid increase in Ca2+ or InsP3 using respective caged compounds indicated that the effects of Ca2+ appear immediately upon change in the Ca2+ concentration. Recovery from the Ca(2+)-dependent inhibition seemed also rapid after reduction in the Ca2+ concentration. These results indicate that there is a Ca(2+)-mediated positive feedback control of InsP3-induced Ca2+ release below 300 nM Ca2+. This feedback control seems to explain, at least partly, the phenomenon that InsP3 is more effective in the Ca2+ stores with greater Ca2+ loading. The Ca(2+)-mediated feedback control is also expected to give rise to temporally or spatially confined Ca2+ release as well as Ca2+ wave within the cells.