Schistosoma transient receptor potential melastatin channel (TRPM_PZQ)

The Schistosoma transient receptor potential melastatin (TRPM_PZQ) channel is a specialized, calcium-permeable ion channel found in parasitic flatworms of the genus Schistosoma, the causative agents of schistosomiasis. Identified in 2019 as the long-sought molecular target of the gold-standard drug praziquantel, this channel is essential for maintaining the parasite's neuromuscular tone and tegumental integrity (Park et al., 2019). Praziquantel binds with nanomolar affinity to a unique hydrophobic pocket in the channel's voltage-sensor-like domain, acting as an allosteric agonist that forces the pore open (Park et al., 2021). The resulting uncontrolled influx of calcium ions causes immediate spastic paralysis and characteristic surface 'blebbing,' which exposes the parasite to the host's immune system (Marchant et al., 2023). Because this specific TRPM variant is unique to schistosomes and closely related trematodes, it provides high therapeutic selectivity with minimal impact on human TRP channels. However, the channel's sequence variation in certain species, such as the liver fluke Fasciola, explains their natural resistance to praziquantel and highlights the importance of this target in monitoring for emerging drug resistance in the field (Rohr et al., 2025).

Other names

SmTRPM_PZQPraziquantel-activated TRP channelSchistosoma mansoni TRPM channelTRPM_PZQSm.TRPM_PZQ

Praziquantel acts as a potent allosteric activator of the Schistosoma TRPM channel by binding to a hydrophobic pocket within its voltage-sensor-like domain. This activation triggers a massive and sustained influx of calcium ions into the parasite's cells, leading to rapid spastic paralysis and severe disruption of the worm's tegument (outer surface).