Acid boosts a scorpion’s sting

The sting of an East Asian Buthidae scorpion causes excruciating pain thanks to more than 100 peptide toxins in its venom. In particular, the 29-amino acid peptide, BmP01, targets one of the most famous pain receptors in mammals, the ion channel called TRPV1, which is better known for being the receptor for capsaicin, the chemical responsible for hot chilies’ burn. But researchers have long puzzled over this conundrum: The concentration of BmP01 required to successfully hit TRPV1 is in the micromolar range, much higher than the levels of the peptide in the scorpion’s venom. So how does the peptide cause so much pain in victims? A team led by Jie Zheng of the University of California, Davis, and Ren Lai of the Chinese Academy of Sciences has an answer. The team reports that in addition to BmP01, protons in scorpions’ acidic venom also help activate TRPV1 (Sci. Adv. 2017, DOI: 10.1126/sciadv.1700810). The researchers note that “BmP01 binds to one of the two proton-binding sites on TRPV1 and, together with a proton, uses a one-two punch approach to strongly activate the nociceptive channel.”