MCD PEPTIDE AND DENDROTOXIN I ACTIVATE C-FOS AND C-JUN EXPRESSION BY ACTING ON 2 DIFFERENT TYPES OF K+ CHANNELS - A DISCRIMINATION USING THE K+ CHANNEL OPENER LEMAKALIM

Mast cell degranulating (MCD) peptide and Dendrotoxin I (DTX(I)), two potent hyperexcitability-inducing toxins acting on voltage-dependent potassium channels, induce the expression of both c-fos and c-jun mRNA in i.c.v. treated rats. The distribution of c-fos and c-jun expression has been analyzed by in situ hybridization. The expression is particularly high in the cerebral cortex and hippocampus for both toxins. However differences of expression between MCD and DTX(I)-treated animals have been observed in hypothalamus and thalamic and amygdaloid nuclei. Moreover, brain areas such as cerebellum which have high amounts of binding sites for both MCD and DTX(I) do not show any induction of c-fos and c-jun. Lemakalim, a K+ channel opener, prevents the MCD-induced activation of both 'immediate-early genes' in all brain areas but is unable to inhibit the induction of c-fos and c-jun induced by DTX(I). These two toxins which are generally believed - from molecular approaches - to act on the same voltage-dependent K+ channel, clearly act in vivo on two distinct classes of channels.