Scolopendra subspinipes mutilans, also known as Chinese red-headed centipede, is a venomous centipede from East Asia and Australasia. Venom from this animal has not been researched as thoroughly as venom from snakes, snails, scorpions, and spiders. In this study, we isolated and characterized SsmTx-I, a novel neurotoxin from the venom of S. subspinipes mutilans. SsmTx-I contains 36 residues with four cysteines forming two disulfide bonds. It had low sequence similarity (<10%) with other identified peptide toxins. By whole-cell recording, SsmTx-I significantly blocked voltage-gated K+ channels in dorsal root ganglion neurons with an IC50 value of 200 nM, but it had no effect on voltage-gated Na+ channels. Among the nine K+ channel subtypes expressed in human embryonic kidney 293 cells, SsmTx-I selectively blocked the Kv2.1 current with an IC50 value of 41.7 nM, but it had little effect on currents mediated by other K+ channel subtypes. Blockage of Kv2.1 by SsmTx-I was not associated with significant alteration of steady-state activation, suggesting that SsmTx-I might act as a simple inhibitor or channel blocker rather than a gating modifier. Our study reported a specific Kv2.1-blocker from centipede venom and provided a basis for future investigations of SsmTx-I, for example on structure–function relationships, mechanism of action, and pharmacological potential. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
SsmTx-I, a novel peptide toxin from the venom of the centipede S subspinipes mutilans, specifically inhibits voltage-gated K+ channel subtype Kv2.1.