Lithium entry into neural cells via sodium channels: a morphometric approach.

Rat cerebral cortical explants prepared from 18-day-old embryos were grown for 18 days in vitro. Cultures were exposed to Na+, Li+ and choline+ media, respectively, in the presence or absence of tetrodotoxin and/or veratridine, and processed for electron-microscopy. Veratridine (50 microM) induced an increase in summated and mean areas of neuronal profiles in Na+- and Li+-media but not in the choline+-medium: the summated perimeters did not change. The mean value of the neuronal form factor was significantly elevated following exposure to veratridine in a Na+- or Li+-dependent manner, indicating that the shape of the sectioned neuronal elements shifted towards an (ideal) circle. Qualitative assessment revealed an increased electron-lucency of the cytoplasm of neuronal profiles in Na+- and Li+-media containing veratridine. The veratridine-induced neuronal changes were inhibited by simultaneous addition of tetrodotoxin (1 microM) to the media. In the case of the glial cells, the values of the summated area and form factor did not change in the various experimental groups. The area of the extracellular space per unit area of sections significantly decreased in the Na+- and Li+-media following veratridine exposure; this did not occur in the choline+-medium. The results indicate a considerable swelling of the neuronal elements, reflecting cation, Cl- and water uptake following prolonged sodium channel activation in the presence of Na+ or Li+ ions. The quantitative ultrastructural data strongly suggests an entry of Li+ ions into cultured rat cerebral cells via sodium channels.