NA,K-ATPASE IS DECREASED IN HIPPOCAMPUS OF KAINATE-LESIONED RATS

The effects of intraventricular injection of kainic acid on the Na,K-ATPase (Na,K pump) were examined in discrete pyramidal cell regions of rat hippocampus. [H-3]Ouabain binding was used to quantitate Na,K-ATPase catalytic subunits and in situ hybridization was used to determine Na,K-ATPase mRNA levels. Large decreases were found in both [H-3]ouabain binding and alpha3 isoform mRNA in hippocampus areas, especially in the CA3 pyramidal cell layer, which sustains heavy cell losses as a result of bilateral, intraventricular injection of kainic acid. Substantial decreases in the high affinity component of ouabain binding and in the alpha3 isoform mRNA (but not isoforms for other Na,K-ATPase subunits) were also observed in the CA1 region of hippocampus, an area preserved in this model. High affinity [H-3]ouabain binding was decreased 25-33% in the stratum pyramidale and stratum radiatum after treatment with kainic acid, and alpha3 mRNA was decreased by 26-50%. To further characterize the decrease in alpha3 mRNA, animals were killed at 1, 2, and 3 weeks after injection of kainate and results show a large decrease in alpha3 mRNA only at 2 weeks recovery time. While the pathology underlying temporal lobe epilepsy is unclear, changes in the Na,K-ATPase may be involved in abnormal firing characteristics of cells in epileptic tissue.