DYNAMIC REGULATION OF THE ACTIVATED, AUTOPHOSPHORYLATED STATE OF CA2+CALMODULIN-DEPENDENT PROTEIN-KINASE-II BY ACUTE NEURONAL EXCITATION IN-VIVO/

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicat ed in various neuronal functions, including synaptic plasticity. To ex amine the physiological regulation of its activated, autophosphorylate d state in relation to acute neuronal excitation in vivo, we studied t he effect of electroconvulsive treatment in rats on CaMKII activity an d in situ autophosphorylation levels. As early as 30 s after the elect rical stimulation, a profound but transient decrease in its Ca2+/calmo dulin-independent activity, as well as in the level of its autophospho rylation at Thr(286) (alpha)/Thr(287) (beta) measured by using phospho rylation state-specific antibodies, was observed in homogenate from hi ppocampus and parietal cortex, which was reversible in 5 min. In the l ater time course, a moderate, reversible increase, which peaked at aro und 60 min after the electrical stimulation, was observed in parietal cortex but not in hippocampus, The early-phase decrease was found to o ccur exclusively in the soluble fraction. In addition, partial translo cation of CaMKII from the soluble to the particulate fraction seems to have occurred in this early phase. Thus, the activated, autophosphory lated state of CaMKII is under dynamic and precise regulation in vivo, and its regulatory mechanisms seem to have regional specificity.