ALUMINUM-INDUCED ALTERATIONS IN [H-3] OUABAIN BINDING AND ATP HYDROLYSIS CATALYZED BY THE RAT-BRAIN SYNAPTOSOMAL (NA-ATPASE(+K+))

The (Na++K+)-ATPase is responsible for maintenance of the ionic milieu of cells. The objective of this study is to investigate the effect of aluminum, an ion implicated in several neurological disorders, on ATP hydrolysis catalyzed by the rat brain synaptosomal (Na++K+)-ATPase an d on the binding of [H-3]ouabain to this enzyme. AlCl3 (25-100 mu M) i nhibits the phosphatase activity of the (Na++K+)-ATPase in a dose-depe ndent manner. AlCl3 appears to act as a reversible, noncompetitive inh ibitor of (Na++K+)-ATPase activity by decreasing the maximum velocity of the enzyme without significantly affecting the apparent dissociatio n constant with respect to ATP. AlCl3 may affect Mg2+ sites on the (Na ++K+)-ATPase but does not appear to interact with Na+ or K+ sites on t he enzyme. In contrast to this inhibitory effect on the phosphatase fu nction of the enzyme, AlCl3 (1-100 mu M) stimulates the binding of [H- 3]ouabain to the (Na++K+)-ATPase. This effect is due to an increase in the maximum [H-3]ouabain binding capacity of the enzyme with no chang e in the [H-3]ouabain binding affinity. These data support the hypothe sis that AlCl3 may stabilize the phosphorylated form of the synaptosom al (Na++K+)-ATPase which increases [H-3]ouabain binding while inhibiti ng the phosphatase activity of the enzyme.