Regulation of c-fos expression by convulsants and hexachlorocyclohexane isomers in primary cultures of cortical neurons.

Primary cortical cultures were used to study the effects of four convulsants on c-fos expression. Approximately 30% of the neurons in these cultures displayed c-fos nuclear immunostaining under basal conditions. The addition of tetrodotoxin, nifedipine, or delta-hexachlorocyclohexane produced a significant decrease in c-fos basal values. Lindane (gamma-hexachlorocyclohexane), Bay K 8644, pentylenetetrazole, and picrotoxinin produced a significant increase in c-fos immunoreactivity and in c-fos mRNA expression. Treatment of cells with tetrodotoxin before administration of the convulsant agents lowered c-fos staining below basal levels. In contrast, delta-hexachlorocyclohexane or nifedipine failed to block only the picrotoxin-induced increase. The differential pattern of expression shown by c-fos after these treatments suggests various mechanisms of action for the compounds studied. The results obtained with delta-hexachlorocyclohexane and nifedipine suggest that picrotoxinin activates c-fos expression by calcium-requiring intracellular signaling pathways that are different from those activated by Bay K 8644, pentylenetetrazole, or gamma-hexachlorocyclohexane, which, at least in part, act via L-type calcium channels.