Margatoxin and iberiotoxin, two selective potassium channel inhibitors, induce c-fos like protein and mRNA in rat organotypic dorsal striatal slices

The isolated single organotypic slice model allows to investigate the effec ts of drugs and toxins on the expression of transcription factors in the st riatum without dopaminergic and glutamatergic interactions. In this study t he effects of margatoxin and iberiotoxin on the expression of c-fos mRNA by in situ hybridization as well as on c-fos like protein by immunohistochemi stry in isolated dorsal striatum after 10 days in culture were investigated . C-fos mRNA dose-dependently increased 30 min after incubation with margat oxin and iberiotoxin. Expression of c-fos like protein was transiently dete cted 3 h afterwards. This effect is independent from extrinsic neuronal cir cuitry as dopamine neurons were found to be absent in the cultured slices. It is concluded that inhibition of voltage-gated as well as calcium-activat ed (Slo) potassium channels leads to activation of gene transcription in st riatal neurons which may trigger long-term changes in transmitter plasticit y.