Lack of effect on brain stem and cerebral cortex Na+, K+-ATPase during heart block produced by chronic digoxin...

The autonomic nervous system has been shown to play an important role in digitalis toxicity. In order to determine whether the central nervous system could be digitalis' site of action, the effect of chronic treatment with toxic doses of digitalis on brain Na+,K+-ATPase was studied in the dog. After four weeks of digoxin treatment, Na+,K+-ATPase activity of the brainstem or cerebral cortex was unaffected at the time when digitalis toxicity (heart block) was apparent. ATP-dependent (3H)-ouabain binding to these tissues was also unaffected indicating that a significant occupancy of brain Na+,K+-ATPase by digoxin did not occur during chronic drug treatment. In contrast, cardiac Na+,K+-ATPase was markedly inhibited with the concomitant binding of digoxin to the enzyme. Since Na+,K+-ATPase is the most digitalis sensitive system identified to date, it appears that digoxin does not affect neuronal function directly.