Two tarantula peptides inhibit activation of multiple sodium channels.

Two peptides, ProTx-I and ProTx-II, from the venom of the tarantula Thrixopelma pruriens, have been isolated and characterized. These peptides were purified on the basis of their ability to reversibly inhibit the tetrodotoxin-resistant Na channel, NaV 1.8, and are shown to belong to the inhibitory cystine knot (ICK) family of peptide toxins interacting with voltage-gated ion channels. The family has several hallmarks:  cystine bridge connectivity, mechanism of channel inhibition, and promiscuity across channels within and across channel families. The cystine bridge connectivity of ProTx-II is very similar to that of other members of this family, i.e., C2 to C16, C9 to C21, and C15 to C25. These peptides are the first high-affinity ligands for tetrodotoxin-resistant peripheral nerve NaV channels, but also inhibit other NaV channels (IC50's < 100 nM). ProTx-I and ProTx-II shift the voltage dependence of activation of NaV 1.5 to more positive voltages, similar to other gating-modifier ICK family members. Pro...