POSSIBLE INVOLVEMENT OF K(ATP) CHANNELS IN THE CONTROL OF 5-HT NEURONS

The possible involvement of ATP-sensitive potassium channels in the co ntrol of the electrical activity of central serotoninergic neurons was investigated by recording their firing rate in the dorsal raphe nucle us of rat brain stem slices exposed to various blockers and openers of these channels. Whereas the channel openers lemakalim and aprikalim p roduced no change in the firing rate of these neurons, the channel blo ckers glibenclamide and gliquidone were strongly inhibitory. As expect ed from an effect through ATP-sensitive potassium channels, the inhibi tion by glibenclamide could be prevented in a competitive manner by le makalim and aprikalim. In contrast, the inactive isomer of the latter drug, RP 61499, did not alter the glibenclamide effect. In addition to the channel openers, the GABA receptor antagonists, bicuculline and p haclofen, but not the antagonist of somato-dendritic 5-HT1A autorecept ors, (-)tertatolol, prevented the negative influence of glibenclamide on the firing rate of serotoninergic neurons. This suggests that GABA acting at both GABA(A) and GABA(B) receptors (but not serotonin throug h the possible stimulation of autoreceptors) was responsible for the e ffect of glibenclamide. Accordingly, the blockade by the latter drug o f ATP-sensitive potassium channels on GABAergic interneurons probably triggered the release of GABA, which in turn, inhibited serotoninergic neurons. In agreement with this hypothetical mechanism, autoradiograp hic studies demonstrated that ATP-sensitive potassium channels are not located on serotoninergic neurons (but probably on GABAergic interneu rons) as the extensive lesion of these neurons by 5,7-dihydroxytryptam ine did not reduce the specific labelling of the dorsal raphe nucleus by [H-3]glibenclamide.