Channels
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Alpha-conotoxins Vc1.1 and RgIA are peptides from the venom of marine Conus snails that are currently in development as a treatment for neuropathic pain. We have reported previously that the alpha9alpha10 nicotinic acetylcholine receptor (nAChR) selective-conotoxins Vc1.1 and RgIA potently and selectively inhibit high voltage-activated (HVA) N-type calcium channel currents in dissociated neurons from rat dorsal root ganglia (DRG). Our data indicated that Vc1.1 does not interact directly with N-type Ca(2+) channels but inhibits them via GABA(B) receptor activation. ⋯ The GABA(B) receptor antagonist CGP55845 (1 microM) antagonized the effect of Vc1.1 and RgIA on the N-type calcium channels in alpha9 KO mice. RT-PCR and western blot analysis confirmed the absence of the alpha9 nAChR in mice carrying a null mutation for the nAChR alpha9 gene. These results demonstrate that the inhibition of N-type Ca(2+) channel channels by Vc1.1 and RgIA is not mediated by the expression of alpha9alpha10 nAChRs in DRG neurons.