BRAIN NA+,K+-ATPASE REGULATION INVIVO - 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-mu-g/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 Rb-86+ 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.