Two mechanisms for spreading depression in the chicken retina

Two mechanisms have been proposed to explain spreading depression (SD): one based on a release of glutamate (Van Harreveld, 1959), and the other on a release of potassium (Grafstein 1956) from neuronal elements. Both glutamate and KCl cause transparency changes in the retina, comparable to those occurring in this tissue during SD. The glutamate effect is inhibited by MgCl2 (10mM), in contrast to the transparency change due to KCl which is not affected by Mg++. Also SD is usually inhibited by MgCl2 which suggests that such SDs are based on a glutamate release. Impairment of the tissue metabolism promotes SDs which are insensitive to MgCl2. The resulting failure of the mechanisms that transport K+ and glutamate which leak out of the intracellular compartment back into the cells and fibers, seems to be involved in the generation of Mg++ insensitive SDs. This may facilitate either K-based SDs or glutamate-based SDs since the inhibitory effect of Mg++ is counteracted by an enhanced glutamate concentration. Both proposed mechanisms for SD seem to be possible under special circumstances.