Selective inhibition of inositol 1,4,5-trisphosphate-induced Ca2+ release in the CA1 region of the hippocampus in the ischemic gerbil

We examined the effect of ischemia on inositol 1,4,5-trisphosphate receptor -induced Ca2+ release by functional and morphological approaches, using the gerbil model after 6-h unilateral occlusion of the common carotid artery. Autoradiographic study revealed that the basal uptake of Ca-45(2+) into the endoplasmic reticulum and caffeine-induced Ca-45(2+) release from the endo plasmic reticulum were normal in the presence of ATP in each ischemic brain region, whereas inositol 1,4,5-trisphosphate receptor-induced Ca-45(2+) re lease from the endoplasmic reticulum was inhibited only in the CAI region o f the hippocampus on the ischemic side. In moderately ischemic gerbils, ele ctron microscopic study demonstrated aggregation of swollen endoplasmic ret iculum in the CAI region of the hippocampus, so that abundant endoplasmic r eticulum assembled in close contact to form endoplasmic reticulum cisternal stacks. In severely ischemic gerbils, immunohistochemical analysis of the hippocampus showed loss of type 1 inositol 1,4,5-trisphosphate receptor pro tein with preservation of immunoreactivity for type 2 and 3 inositol 1,4,5- trisphosphate receptor proteins, which was confirmed by western blot analys is. Such selective inhibition of inositol 1,4,5-trisphosphate receptor-induced Ca2+ release and the loss of type 1 inositol 1,4,5 trisphosphate receptor i n the CA1 region of the hippocampus in cerebral ischemia may be associated with its region-specific vulnerability to ischemia. (C) 1999 IBRO. Publishe d by Elsevier Science Ltd.