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• W4313593766 startingPage "415" @default.
• W4313593766 abstract "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 TRPMPZQ - is a Ca2+-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 TRPMPZQ channel (Sm.TRPMPZQ) in response to PZQ. Single channel electrophysiological analysis demonstrated that Sm.TRPMPZQ when activated by PZQ is a non-selective, large conductance, voltage-insensitive cation channel that displays distinct properties from human TRPM paralogs. Sm.TRPMPZQ is Ca2+-permeable but does not require Ca2+ for channel gating in response to PZQ. TRPMPZQ from Schistosoma japonicum (Sj.TRPMPZQ) and Schistosoma haematobium (Sh.TRPMPZQ) displayed similar characteristics. Profiling Sm.TRPMPZQ responsiveness to PZQ has established a biophysical signature for this channel that will aid future investigation of endogenous TRPMPZQ activity, as well as analyses of endogenous and exogenous regulators of this novel, druggable antiparasitic target." @default.
• W4313593766 created "2023-01-06" @default.
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• W4313593766 date "2023-07-01" @default.
• W4313593766 modified "2023-09-29" @default.
• W4313593766 title "Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel" @default.
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• W4313593766 doi "https://doi.org/10.1016/j.ijpara.2022.11.005" @default.
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