Effect of intermittent mild hypoxia and drug treatment on synaptosomal nonmitochondrial ATPase activities

Abstract

Synaptosomal nonmitochondrial ATPases linked to the energy-utilizing systems were evaluated in cerebral cortex from normoxic rats and rats submitted to mild intermittent normobaric hypoxia [12 hr daily exposure to N2:O2 (90:10) mixture for 4 weeks]. The activities of Na+,K(+)-ATPase; high- and low-affinity Ca(2+)-ATPase; basal Mg(2+)-ATPase; and Ca2+, Mg(2+)-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely, synaptosomal plasma membranes and synaptic vesicles. The evaluations were performed either in normoxic rats or in hypoxic rats submitted to 4-week treatment with saline (controls) or a vasodilator agent (papaverine), an energy-metabolism interfering agent (theniloxazine), a calcium blocker (nicardipine), and a lipid-metabolism interfering agent (phosphatidylcholine) in order to define the plasticity and the selective changes in individual ATPases. In synaptosomes from rat cerebral cortex, the enzyme adaptation to the daily mild intermittent hypoxia for 4 weeks was characterized by an increase in the activity of Mg(2+)-ATPase, concomitant with a decrease in the activities of Na+,K(+)-ATPase, high-affinity Ca(2+)-ATPase, and Ca2+, Mg(2+)-ATPase. In hypoxic rats the enzyme adaptation to the 4-week treatment with phosphatidylcholine was characterized by an increase in Ca2+, Mg(2+)-ATPase activity and a decrease in Mg(2+)-ATPase activity. The action involves the enzymatic form located in the synaptic plasma membranes. In hypoxic rats the adaptation to the 4 week treatment with nicardipine was characterized by an increase in high-affinity Ca(2+)-ATPase activity, while the 4-week-treatment with theniloxazine induced an increase in Na+,K(+)-ATPase activity. The actions of both nicardipine and theniloxazine were related to the enzymatic forms located in the synaptic plasma membranes. The effects on the biophase induced by the sequential cycles of hypoxia/normoxia and the treatment with the various agents tested should also be related to the changes induced in the activity of some synaptosomal ATPases.