Seizures in Rats Associated with Divalent Cation Inhibition of Na⁺–K⁺-ATP'ase

Abstract

In vitro determination of rat brain microsomal ATP'ase activity revealed specific inhibition of the Na + –K + -ATP'ase by cations in the order Zn 2+ > Cu 2+ > Fe 2+ > Mn 2+ . Intraventricular injection of the same cations or of ouabain resulted in convulsions. Regional analysis of ATP'ase from brains of rats after convulsions showed inhibited Na + –K + -ATP'ase activity in hippocampus and hypothalamus. Hippocampus and hypothalamus were found to have the highest Na + –K + -ATP'ase activity in the rat brain.The potent inhibitors of Na + –K + -ATP'ase in vitro (ouabain, Zn 2+ , and Cu 2+ ) were similarly effective in vivo (hippocampus and hypothalamus), while the inhibitors relatively ineffective in vitro (Fe 2+ and Mn 2+ ) were similarly of low potency in vivo. The potent inhibitors of Na + –K + -ATP'ase caused convulsions at low doses; the ineffective inhibitors caused convulsions only at very high doses.