Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel.

Ion channels have proved to be productive targets for anthelmintic chemotherapy. One example is the recent discovery of a parasitic flatworm ion channel targeted by praziquantel (PZQ), the main clinical therapy used for treatment of schistosomiasis. The ion channel activated by PZQ - a transient receptor potential ion channel of the melastatin subfamily, named TRPM - is a Ca-permeable ion channel expressed in all parasitic flatworms that are PZQ-sensitive. However, little is currently known about the electrophysiological properties of this target that mediates the deleterious action of PZQ on many trematodes and cestodes. Here, we provide a detailed biophysical characterization of the properties of Schistosoma mansoni TRPM channel (Sm.TRPM) in response to PZQ. Single channel electrophysiological analysis demonstrated that Sm.TRPM when activated by PZQ is a non-selective, large conductance, voltage-insensitive cation channel that displays distinct properties from human TRPM paralogs. Sm.TRPM is Ca-permeable but does not require Ca for channel gating in response to PZQ. TRPM from Schistosoma japonicum (Sj.TRPM) and Schistosoma haematobium (Sh.TRPM) displayed similar characteristics. Profiling Sm.TRPM responsiveness to PZQ has established a biophysical signature for this channel that will aid future investigation of endogenous TRPM activity, as well as analyses of endogenous and exogenous regulators of this novel, druggable antiparasitic target.