Specific distribution of Ca2+/calmodulin-dependent protein kinase II alpha and beta isoforms in some structures of the rat forebrain.

The immunohistochemical distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha and beta isoforms in the rat forebrain was examined by using monoclonal antibodies specific to each isoform. The present study confirmed that alpha and beta immunoreactivities are localized only in neuronal elements. At the light microscopic level, specific distribution patterns of these isoforms and staining characteristics were recognized in some regions of the forebrain as follows. Firstly, alpha-immunoreactive neurons were more homogeneously distributed throughout the cellular layers of the cerebral cortex (i.e., layers II-VI) than beta-immunoreactive ones. Secondly, neurons in the globus pallidus were immunostained by the anti-beta antibody, but not by the anti-alpha antibody. Thirdly, neurons in the medial habenular nucleus, the subthalamic nucleus and the reticular thalamic nucleus were more densely stained with the anti-beta antibody than with the anti-alpha antibody. However, marked differences were not observed in the hippocampal formation at the light microscopic level. The electron microscopic analysis of the cerebral cortex demonstrated that subcellular localizations of alpha- and beta-immunoreactive products within the cortical neurons were quite dissimilar: (i) the nucleus was stained only with the anti-alpha antibody, but not with the anti-beta antibody, and (ii) beta-immunoreactive products were more sporadically localized in the cytoplasms of the perikarya and dendrites than the alpha-immunoreactive ones. These regional and subcellular differences between the distribution patterns of alpha and beta immunoreactivities suggest the functional diversity of CaM kinase II alpha and beta isoforms in the central nervous system.