EDTA and EGTA stimulate 36Cl- uptake into rat brain synaptoneurosomes.

Addition of EDTA (0.5-10 mM) to rat brain synaptoneurosomes stimulated rapid, concentration-dependent uptake of 36C1-. Chloride uptake stimulated by EDTA was additive with the 36C1- uptake induced by the GABAA agonist, muscimol, and was not blocked by the GABA-antagonist, picrotoxin, the glycine antagonist, strychnine or the loop diuretic, furosemide. However, the chloride transport inhibitor DIDS completely antagonized 36C1- uptake. EDTA-induced 36C1- uptake varied across brain regions as follows: Striatum greater than hippocampus greater than cerebellum greater than tectum greater than cerebral cortex greater than brain stem greater than hypothalamus. EDTA-induced 36C1- uptake was also present in liver tissues. EDTA analogues, EGTA and CDTA, also stimulated uptake. Although the effect of EDTA was dependent on the presence of extravesicular Ca2+ (0.01-10 mM) this action did not appear to be due to Ca2+ chelation since BAPTA, arsenazo III and citrate were ineffective. These results suggest that EDTA stimulates 36C1- uptake into brain synaptoneurosomes by a picrotoxin-insensitive, calcium-dependent mechanism that may involve a DIDS sensitive anion exchanger or ion channel.