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Frog sciatic nerves were incubated for 24 hours in either glycine, aspartic acid, glutamic acid, lysine, leucine, y-aminobutyric acid, glutamine, or pentanedioic acid (all labeled with C14), and the rates of release of these compounds were monitored under resting conditions and during stimulation. Upon stimulation, the rate or release of glutamic acid increased an average of 200% above the resting rate. This extra release is highly specific with regard to molecular size and structure, since of the compounds tested only glutamic acid gave significant increases in rates of release during stimulation. Ouabain (0.1 mM) had no effect on the rate of release; however, sodium azide (0.2 mM or 1.0 mM) completely eliminated the extra release during excitation, indicating that the increased permeability to glutamic acid is energy-dependent. Competition experiments show that the extra release of glutamic acid can be eliminated with 10 mM concentrations of non-isotopic choline.The hypothesis is advanced that glutamic acid is actively extruded by a highly specific carrier mechanism.

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