Long-lasting decreases of type II calmodulin kinase expression in kindled rat brains.

The kindling model of epilepsy is associated with long-lasting changes in type II calmodulin kinase (CaM kinase) activity and immunoreactivity. In order to determine the mechanism of these alterations, we measured gene expression of CaM kinase using in situ hybridization in septally kindled rat brains and paired controls using a 35S-labeled riboprobe for the beta subunit of the enzyme. We found CaM kinase mRNA concentrated in the hippocampus and other limbic structures. Kindling decreased hippocampal CaM kinase mRNA by 30% in CA1, 34% in CA2, 35% in CA3 41% in CA4, and 29% in the dentate gyrus. Hybridization was also decreased by 21% in the cerebral cortex but not in the lateral septum. These changes are similar in distribution and direction to those previously measured by immunohistochemistry. These data suggest that altered CaM kinase activity and immunoreactivity associated with kindling reflect long-lasting alterations in gene expression of this important synaptic protein, and provide further evidence for its possible importance in the kindling phenomenon.