Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPM PZQ .

The parasitic flatworm ion channel, TRPM, is a non-selective cation channel that mediates Ca entry and membrane depolarization when activated by the anthelmintic drug, praziquantel (PZQ). TRPM is conserved in all platyhelminth genomes scrutinized to date, with the sensitivity of TRPM in any particular 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 TRPM 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. TRPM is therefore a multimodal ion channel gated by both physical and chemical cues. The mechanosensitivity of TRPM is one route for endogenous activation of this ion channel that holds relevance for schistosome physiology given the persistent pressures and mechanical cues experienced throughout the parasite life cycle.