ACIDOSIS-INDUCED MODIFICATIONS OF HIGH-AFFINITY CHOLINE UPTAKE BY SYNAPTOSOMES - EFFECTS OF PH READJUSTMENT

Acidosis (pH 6.0) led to significant decrease in high-affinity choline uptake by rat brain synaptosomes. The effects persisted following pH readjustment (7.4) of the incubation medium, consisting of decrease in both Km and Vmax of the affinity system. pH readjustment coincided wi th synaptosomal leakage of lactate dehydrogenase (LDH) and with instab ility of the synaptosomal suspension as evidenced from turbidity modif ications of the preparation. LDH leakage occurred when acidosis was pe rformed with lactic acid, whereas it was not seen following H3PO4 acid osis, probably because of the rapid diffusion of the protonated form o f lactic acid across membranes. Turbidity modifications of the suspens ion were prevented by EDTA. The present results indicate that acidosis to pH level comparable to what is observed in brain ischemia is delet erious for cholinergic mechanisms. They also suggest that alkaline pH shifts that occur after blood reperfusion of ischemic brain tissue mig ht be critical for the survival of cells.