Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+,K+-ATPase inhibitors

Abstract

The effects of iontophoretically applied Na⁺-,K⁺-dependent adenosinetriphosphatase (Na⁺,K⁺-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by γ-aminobutyric acid, adenosine, adenosine 5′-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na⁺,K⁺-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.