Excitatory acidic amino acids and the cation content and sodium ion flux of isolated tissues from the brain.

1. Sample from the neocortex and piriform cortex of guinea pigs and rats were incubated in inulin-containing glucose-saline. Their intracellular (non-inulin) space contained 19-27muequiv. of Na(+)/g. of original tissue. These values were stable between 30 and 100min. after incubation commenced, but addition of (22)NaCl to the neocortical samples showed them to be associated with a flux of 400muequiv. of Na(+)/g. of tissue/hr. 2. Addition of 0.5-10mm-l-glutamic acid or 0.1mm-N-methyl-dl-aspartic acid rapidly increased the tissue's Na(+) content; N-acetyl-dl-aspartic acid was without action. 3. During the first 1-1.5min. after the addition of l-glutamic acid to neocortical samples their Na(+) content increased at 600muequiv./g. of tissue/hr., and the rate of (22)Na(+) influx corresponded to 1230muequiv. of Na(+)/g./hr. These rates were calculated to be sufficiently rapid to account for loss of the tissue's normal membrane potential within 1-2sec. of the addition of the acid. 4. In addition, a rapid but more limited loss of K(+) took place after the addition of l-glutamic acid or the methylaspartic acid; on continued incubation tissue K(+) content increased, as also did the intracellular volume of the tissue, from its original 670mul./g. to 1100mul./g. 5. Interpretation of these and of associated changes is offered in terms that involve a cation pump and the permeability changes associated with the nerve impulse.