The role of chloride in acetylcholine metabolism.

The chloride dependence of acetylcholine (ACh) synthesis and release and of choline uptake was studied in synaptosomal preparations from rat brain. The substitution of propionate for chloride, in the presence of 35 mM-potassium, lowered the ACh content of the synaptosomes. However, in the presence of 5 mM-potassium, the ACh level in synaptosomes was reduced, but significantly less so. Propionate had no effect on choline acetyltransferase (EC 2.3.1.6) activity when measured in a standard chloride-containing medium. In the presence of propionate, the spontaneous release of ACh was unchanged, but potassium-stimulated release of ACh was markedly reduced as compared with a chloride-containing medium. The synthesis of ACh, as measured by the net increase in the amount of ACh in the synaptosomes and that released to the medium, was reduced with propionate at 5 mM-potassium and was totally inhibited when the potassium concentration was increased to 35 mM. Choline uptake studies revealed that with propionate only a low-affinity component of the choline transport system existed. Further, the Vmax was markedly reduced when the potassium concentration was increased to 35 mM. The results suggest that under certain conditions choline transported by a low-affinity system might provide a substantial source of choline for ACh synthesis.