Mechanisms involved in spreading depression

Application of unlabelled glutamate to the isolated chicken retina caused an increase in the tissue transparency and a release of labelled glutamate with which the retina had previously been charged. The threshold for both responses was about 0.2 mM. Stimulation with KCI and direct current elicited transparency changes at a threshold of 8 mM and 4–6 V, respectively, and a release of the label at higher KCl concentrations (75 mM) and potentials (15 V). The transparency change caused by glutamate stimulation was severely depressed by MgC12 (10–15 mM) in contrast to the changes elicited by KC1 and direct current which were little affected by Mg ions. It was postulated that glutamate causes transparency changes by acting on neuronal elements. KC1 would act on glia and would only in high concentrations affect neurons. It was furthermore suggested that the propagation of spreading depression is dependent both on the release of glutamate from the intracellular compartment and on the depolarization of neuronal elements resulting from this release.