Inositol 1,4,5-trisphosphate induced mobilization of Ca2+ from rat brain synaptosomes

Abstract

Inositol 1,4,5-trisphosphate (IP3) was found to release Ca2+ from presynaptic nerve endings (synaptosomes) made permeable with saponin. ATP-dependent Ca2+ uptake was carried out until equilibrium was reached. Addition of IP3 produced a rapid release of Ca2+, which was complete within 60 sec, followed by Ca2+ reaccumulation to the original level in 5-7 min. Cholinergic receptor stimulation with muscarine also produced a similar Ca2+ release from synaptic endoplasmic reticulum. Ca2+ release by IP3 was not detectable in the absence of the mitochondrial inhibitors oligomycin or sodium azide. Reaccumulation of Ca2+ was prevented by the presence of vanadate, a potent inhibitor of Ca2+/Mg2+ ATPase. Half maximal and near complete release of Ca2+ took place at 0.4 microM and 3 microM IP3 concentrations, respectively. These studies demonstrate for the first time IP3 mobilization of Ca2+ from endoplasmic reticulum within synaptic plasma membranes.