VISUALIZATION OF THE DISTRIBUTION OF AUTOPHOSPHORYLATED CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II AFTER TETANIC STIMULATION IN THE CA1AREA OF THE HIPPOCAMPUS

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+ independent kinase activity an d has been proposed to be involved in induction of long-term potentiat ion by tetanic stimulation in the hippocampus. We have used an immunoc ytochemical method to visualize and quantify the pattern of autophosph orylation of CaMKII in hippocampal slices after tetanization of the Sc haffer collateral pathway. Thirty minutes after tetanic stimulation, a utophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In a pical dendrites, this increase is accompanied by an equally significan t increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the tot al amount of CaMKII. In neuronal somas, however, the increase in P-CaM KII is not accompanied by an increase in the total amount of CaMKII. W e suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, howe ver, tetanic stimulation appears to result in long-lasting increases i n P-CaMKII independent of an increase in the total amount of CaMKII. O ur findings are consistent with a role for autophosphorylation of CaMK II in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activi ty are not confined to synapses and may involve induction of new synth esis of kinase in dendrites as well as increases in the level of autop hosphorylated kinase.