IS THE MG2-ATP-DEPENDENT PROTON-PUMPING ACTIVITY OF THE SYNAPTIC VESICLES A FACTOR INVOLVED IN THE CEREBRAL HYPOXIA()

The changes in the Mg2+-dependent V-type ATPase activity and the Mg2+- ATP-dependent H+ pumping activity of the synaptic vesicles from the ce rebral cortex of rats submitted to intermittent chronic (4 weeks) mild or severe hypoxia were evaluated. The adaptation to the chronic sever e hypoxia increases both the ATPase and the H+ pumping activities whic h are inhibited by NEM with an exponential relationship between the IC 50 values and the in vivo O-2 concentration. The Mg2+-dependent increa se in Hi pumping activity of synaptic vesicles from the rats subjected to in vivo chronic hypoxia may be antagonized by nigericin (dissipati ng Delta pH) and by FCCP (dissipating Delta pH and Delta(psi sv)). In contrast, valinomycin (dissipating the Delta(psi sv) and facilitating an enhancement in Delta pH) increases in vitro the H+ pumping activity that is inhibited by the addition of high concentration of K gluconat e (reducing the rate of K+ efflux). The preincubation of vesicles from hypoxic rats with FCCP, but not with nigericin, inhibits the valinomy cin-increased H+ pumping activity. L-glutamate increases the H+ pumpin g activity in synaptic vesicles from the cerebral cortex of chronic hy poxic rats, whereas other amino acids (i.e., L-aspartate and L-homocys teate) and glutamate analogs (i.e., quisqualate and ibotenate) are ine ffective. The adaptation to both chronic intermittent severe hypoxia a nd in vivo treatment with posatireline causes a decrease in the Mg2+-A TPase activity consistent with the decrease in the H+ pumping one of t he synaptic vesicles. The addition of nigericin into incubation medium magnifies the decrease in the H+ pumping activity, while the addition of FCCP is ineffective, suggesting that the treatment with posatireli ne interferes with the Delta(psi sv) component in the Delta<(mu)over t ilde (H+)> of the synaptic vesicles from rats submitted to chronic hyp oxia. The results of the in vivo and in vitro experiments suggest that in the synaptic vesicles from hypoxic rats the Delta(psi sv) componen t in Delta<(mu)over tilde (H+)> may be most effective in increasing th e Mg2+-ATP-dependent H+ pumping activity.