Brain Na+,K(+)-ATPase regulation in vivo: reduction in activity and response to sodium by intracerebroventricular tetrodotoxin.
We investigated the effects of intracerebroventricular infusion of tetrodotoxin on activity and function of brain Na+,K(+)-ATPase. Infusion of 1 or 3 micrograms/h for 2, 4 or 7 days by osmotic minipump reduced the number of Na+,K(+)-ATPase sites as measured by ouabain binding in cerebral cortex. Tetrodotoxin infusions substantially reduced the functional transport capacity of Na+,K(+)-ATPase, measured by the maximal increase in synaptoneurosomal 86Rb+ uptake in the presence of monensin. The effects were maximal at 4 days, with a possible partial recovery of activity at 7 days. Results of ouabain inhibition curves suggested that the effect of tetrodotoxin was not specific for enzyme with high or low affinity for ouabain.
Swann
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AC
Department of Psychiatry, University of Texas Medical School, Houston 77225.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D007276:Injections, Intraventricular; D008297:Male; D008985:Monensin / Q000494:pharmacology; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology*
D012414:Rubidium Radioisotopes; D013779:Tetrodotoxin; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase