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. [3H]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 [3H]ouabain binding and alpha 3 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 alpha 3 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 [3H]ouabain binding was decreased 25-33% in the stratum pyramidale and stratum radiatum after treatment with kainic acid, and alpha 3 mRNA was decreased by 26-50%. To further characterize the decrease in alpha 3 mRNA, animals were killed at 1, 2, and 3 weeks after injection of kainate and results show a large decrease in alpha 3 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.
Neurochemistry Lab., Veterans Affairs Medical Center, Seattle, WA 98108.
W R
WR
Anderson
J E
JE
Franck
W L
WL
Stahl
A A
AA
Maki
D000818:Animals; D001345:Autoradiography; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D010042:Ouabain / Q000493:pharmacokinetics; D017966:Pyramidal Cells / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D012333:RNA, Messenger; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D007608:Kainic Acid