A naturally-occurring carboxyl-terminally truncated α-scorpion toxin is a blocker of sodium channels.

α-Scorpion toxins constitute a multigene family of evolutionarily conserved venom peptides that inhibit sodium channel inactivation and increase its peak current. Here, we describe the characterization of a new α-scorpion toxin gene expressed in the venom gland of Mesobuthus eupeus that encodes a carboxyl-terminally truncated product of 38 residues (named MeuNaTxα(NT)-1). Synthetic MeuNaTxα(NT)-1 was oxidized to form two disulfide bridges in an alkaline environment and the refolded peptide exhibits different structure and function from the classical α-scorpion toxin. MeuNaTxα(NT)-1 blocks sodium channels on rat dorsal root ganglia (DRG) neurons without impact on the inactivation of the channels. This work provides a clue for evolution-guided design of channel blockers for therapeutic aims.