Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPMPZQ

The parasitic flatworm ion channel, TRPMPZQ, is a non-selective cation channel that mediates Ca2+entry and membrane depolarization when activated by the anthelmintic drug, praziquantel (PZQ). TRPMPZQ is conserved in all platyhelminth genomes scrutinized to date, with the sensitivity of TRPMPZQ in any par-ticular flatworm correlating with the overall sensitivity of the worm to PZQ. Conservation of this channel suggests it plays a role in flatworm physiology, but the nature of the endogenous cues that activate this channel are currently unknown. Here, we demonstrate that TRPMPZQ is activated in a ligand-independent manner by membrane stretch, with the electrophysiological signature of channel opening events being identical whether evoked by negative pressure, or by PZQ. TRPMPZQis therefore a multimodal ion channel gated by both physical and chemical cues. The mechanosensitivity of TRPMPZQ is one route for endoge-nous activation of this ion channel that holds relevance for schistosome physiology given the persistent pressures and mechanical cues experienced throughout the parasite life cycle.& COPY; 2022 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.