PERSISTENT TRANSLOCATION OF CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE-II TO SYNAPTIC JUNCTIONS IN THE VULNERABLE HIPPOCAMPAL CA1 REGION FOLLOWING TRANSIENT ISCHEMIA/

The influence of brain ischemia on the subcellular distribution and ac tivity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) was studied in various cortical rat brain regions during and after cer ebral ischemia. Total CaM kinase II immunoreactivity (IR) and calmodul in binding in the crude synaptosomal fraction of all regions studied i ncrease but decrease in the microsomal and cytosolic fractions, indica tive of a translocation of CaM kinase II to synaptosomes. The transloc ation of CaM kinase II to synaptic junctions occurs but not to synapti c vesicles. The translocation in neocortex and CA3/DG (dentate gyrus) is transient, whereas in the hippocampal CAI region, it persists for a t least 1 day of reperfusion. The Ca2+/calmodulin-dependent activity o f CaM kinase II in the subsynaptosomal fractions of neocortex is persi stently decreased by up to 85%, despite the increase in CaM kinase II IR. The decrease in activity is more pronounced than the decline in IR , suggesting that CaM kinase II is covalently modified in the postisch emic phase. The persistent translocation of CaM kinase II in the vulne rable ischemic CA1 region indicates that a pathological process is sus tained in the area after the reperfusion phase and this may be of sign ificance for ischemic brain injury.