Calcium-dependent immediate feedback control of inositol 1,4,5-triphosphate-induced Ca2+ release

Abstract

The temporal and spatial distribution of increases in intracellular Ca2+ concentration is an important factor in cellular signal transduction. Inositol 1,4,5-trisphosphate (InsP3) plays a key part in agonist-induced Ca2+ release, which can take place abruptly and in a confined space by a mechanism that is not fully understood. Here we analyse the kinetics of InsP3-induced Ca2+ release following flash photolysis of caged InsP3 or caged Ca2+, and demonstrate that Ca(2+)-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+ release. Furthermore, our results support the operation of positive cooperativity in channel opening 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.