CALCIUM-DEPENDENT IMMEDIATE FEEDBACK-CONTROL OF INOSITOL 1,4,5-TRISPHOSPHATE-INDUCED CA2+ RELEASE

THE temporal and spatial distribution of increases in intracellular Ca2+ concentration is an important factor in cellular signal transduction1. Inositol 1,4,5-trisphosphate (InsP3) plays a key part in agonist-induced Ca2+ release1, which can take place abruptly2 and in a confined space3 by a mechanism that is not fully understood. Here we analyse the kinetics of InsP3-induced Ca2+ release following flash photolysis4-7 of Caged InsP3 or caged Ca2+, and demonstrate that Ca2+-dependent immediate feedback control is an important determinant of the time course of Ca2+ release. The positive feedback mechanism is also important for the 'loading dependence' of InsP3-induced Ca2+ release8. Furthermore, our results support the operation of positive cooperativity in channel opening9 and feedback control augments the steep InsP3 concentration-Ca2+ release relation. These inherent properties of InsP3-induced Ca2+ release are expected to give rise to temporally abrupt and/or spatially confined Ca2+ release within the cell.