Phosphorylation of brain (Na+,K+)-ATPase alpha catalytic subunits in normal and epileptic cerebral cortex: I. The audiogenic mice and the cat with a freeze lesion.
Partially purified (Na+,K+)-ATPase (E.C. 3.6.1.3.) was investigated in the epileptic cortex of audiogenic DBA/2 mice and in the primary and secondary foci of cats with acute or chronic freeze lesions. No differences in specific activities measured at 3 mM K+ were observed between epileptic and control cortex, except an increase of enzymic activities in the primary focus of acutely lesioned cats. The (Na+,K+)-ATPase catalytic subunits were resolved by SDS-gel electrophoresis and their phosphorylation levels were measured in presence of K+ ions and phenytoin. K+ was more effective in inducing maximal dephosphorylation of (Na+,K+)-ATPase in C57/BL, with identical affinity in the two strains. Phenytoin decreased the net phosphorylation level of (Na+,K+)-ATPase by about 50% in C57/BL mice, but only by 20% in DBA/2 mice. Both K+ and phenytoin dephosphorylating influences were decreased in primary and secondary foci of acutely lesioned cats. Those changes were limited to the alpha(-) subunit. In chronic cats, the dephosphorylating step of the (Na+,K+)-ATPase catalytic subunit recovered a normal affinity to K+, but its sensitivity to phenytoin remained decreased. Those differences in K+ and phenytoin influences on brain (Na+,K+)-ATPases between control and epileptic cortex might be responsible for the ictal transformation and seizure spread. In cats, the alteration of the alpha(-) isoform could mainly affect the glial cells.
Guillaume
D
D
Molecular Neuroscience Laboratories, Reed Neurological Research Center, University of California, Los Angeles.
Grisar
T
T
Delgado-Escueta
A V
AV
Bureau-Heeren
M
M
Laschet
J
J
D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002384:Catalysis; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004827:Epilepsy / Q000378:metabolism*; D005615:Freezing; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D010672:Phenytoin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium