Transient receptor potential melastatin channel (TRPMPZQ) (TRPMPZQ)

The Transient receptor potential melastatin channel (TRPMPZQ) is a calcium-permeable, non-selective cation channel found in parasitic flatworms, including schistosomes and tapeworms (Park and Marchant, 2020). For over 40 years, the molecular target of the primary anthelmintic drug praziquantel was unknown and was generically referred to as the "parasite calcium channel" or hypothesized to be a subunit of voltage-gated calcium channels (Park et al., 2019). In 2019, TRPMPZQ was identified as the definitive target, where praziquantel acts as a potent and stereoselective agonist (Park et al., 2019). Activation of TRPMPZQ triggers a massive, sustained influx of calcium ions into the parasite's nervous system and muscles, resulting in immediate spastic paralysis and catastrophic disruption of the parasite's tegument (Chulkov et al., 2021). This tegumental damage is critical for therapeutic efficacy, as it exposes the parasite to the host's immune system, leading to its clearance (Park and Marchant, 2020). While TRPMPZQ is highly conserved across many sensitive species, natural variations in the channel's binding pocket, such as the N-to-T mutation found in Fasciola hepatica, render certain parasites inherently resistant to praziquantel (Park et al., 2021). The discovery of this specific channel has shifted the focus from generic calcium signaling to target-based drug discovery for neglected tropical diseases (Marchant, 2024).

Other names

SmTRPMPZQSchistosome calcium channelPraziquantel targetParasite calcium channelFlatworm TRPM channelVoltage-gated calcium channel beta subunit (historical)

Agonist (activator) of the TRPMPZQ channel, inducing rapid calcium influx, spastic paralysis, and tegumental disruption.