The venom of the Australian Black Rock scorpion induces pain in a unique way.

King et al. in their new article in the current issue of Cell published their discovery of a cell-penetrating peptide isolated from the venom of the Australian Black Rock scorpion.

This venom activates the TRPA1 receptor in a unique way to induce pain. The Trp receptor family represents a diverse group of non-selective cation channels that function primarily in sensory physiology. Different Trp channels are expressed on peripheral neurons and their activation by exogenous stimuli contributes to the transmission of pain. King and colleagues report here for the first time a peptide component in the venom of the scorpion, Urodacus manicatus, commonly known as the Australian Black Rock scorpion, that activates the TRPA1 ion channel.

The active component, wasabi receptor toxin (WaTx), was identified using high-performance liquid chromatography (HPLC) and mass spec, uncovering a similar 1-4, 2-3 disulfide bonding pattern found in venoms of other scorpion species. They describe how WaTx activates TRPA1 by penetrating the plasma membrane to access the same intracellular site modified by reactive electrophiles. WaTx stabilizes TRPA1 in a biophysically distinct active state characterized by prolonged channel openings and low Ca 2+ permeability. Consequently, WaTx elicits acute pain and pain hypersensitivity but fails to trigger efferent release of neuropeptides and neurogenic inflammation typically produced by noxious electrophiles. These findings provide a striking example of convergent evolution whereby chemically disparate animal- and plant-derived irritants target the same key allosteric regulatory site to differentially modulate channel activity. WaTx is a unique pharmacological probe for dissecting TRPA1 function and its contribution to acute and persistent pain.

Reference- Cell 178, September 5, 2019