Conotoxins of the O-superfamily affecting voltage-gated sodium channels

The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized by a conserved cysteine knot pattern: C-C-CC-C-C. While omega-conotoxins and kappa-conotoxins block Ca(2+) and K(+) channels, respectively, the closely related delta- and microO-conotoxins affect voltage-gated Na(+) channels (Na(v) channels). delta-conotoxins mainly remove the fast inactivation of Na(v) channels and, thus, functionally resemble long-chain scorpion alpha-toxins. microO-conotoxins are functionally similar to micro-conotoxins, since they inhibit the ion flow through Na(v) channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms. Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Na(v) channels.