Effect of elevated extracellular potassium on the release of labelled noradrenaline, glutamate, glycine, β-alanine and other amino acids from rat brain cortex slices

Abstract

The effect of an elevated concentration (46 m m) of extracellular potassium on the release, from superfused rat brain cortex slices, of labelled γ-aminobutyrate, glutamate, glycine, α- and β-alanine, aspartate, taurine and α-aminoisobutyrate has been studied; and a comparison made with the release of soluble (non-vesicular) noradrenaline (i.e. that transported into slices taken from the brains of animals pretreated with reserpine; the slices were incubated with nialamide). In all cases, with the possible exception of l-α-alanine, elevated potassium induced an increased efflux of these substances. Omission of calcium in the superfusing fluid markedly diminished the release of all the test substances, except, in part, that of β-alanine. It was also found that the time course of the induced efflux varied considerably for the different substances: substances such as noradrenaline and γ-aminobutyrate that are transported predominantly into axons and axon terminals, showed a ‘peak’ time course, with a maximal release within 2–4 min following potassium elevation, and the rate of release diminished rapidly in spite of the continued presence of high potassium. Such a decreased release was not due to exhaustion of the tissue stores of these substances. On the other hand, glutamate and glycine, substances that are thought to be transported predominantly into glial cells, attained their maximal release rates only 10 min after potassium was elevated, and such release was maintained without decrement, β-alanine showed a mixed type of release, with a small initial peak resembling that of the axonally located substances, and a delayed release similar to that of glycine and glutamate. The release of the rest of the amino acids also resembled that of glycine and glutamate. A correlation was found ( r = 0.99, P < 0.01) between the area of the efflux curve that had a ‘peak’ shape, and the percentage of the substance that was transported into an axonal compartment. It is concluded that although elevated potassium concentrations can release substances from both axons and glia, and that a calcium dependency may exist in both cases, the time course of the induced efflux is markedly different when the substances are located in axons or in glial cells. Such a procedure may prove valuable for establishing grossly into which compartment a given substance is transported.