Faculty Collaboration Database

Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel. Int J Parasitol 2023 Jul;53(8):415-425

Date

01/08/2023

Pubmed ID

36610556

Pubmed Central ID

PMC10258134

DOI

10.1016/j.ijpara.2022.11.005

Scopus ID

2-s2.0-85146083227 (requires institutional sign-in at Scopus site)   2 Citations

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 TRPM_PZQ - 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 TRPM_PZQ channel (Sm.TRPM_PZQ) in response to PZQ. Single channel electrophysiological analysis demonstrated that Sm.TRPM_PZQ when activated by PZQ is a non-selective, large conductance, voltage-insensitive cation channel that displays distinct properties from human TRPM paralogs. Sm.TRPM_PZQ is Ca²⁺-permeable but does not require Ca²⁺ for channel gating in response to PZQ. TRPM_PZQ from Schistosoma japonicum (Sj.TRPM_PZQ) and Schistosoma haematobium (Sh.TRPM_PZQ) displayed similar characteristics. Profiling Sm.TRPM_PZQ responsiveness to PZQ has established a biophysical signature for this channel that will aid future investigation of endogenous TRPM_PZQ activity, as well as analyses of endogenous and exogenous regulators of this novel, druggable antiparasitic target.

Author List

Chulkov EG, Palygin O, Yahya NA, Park SK, Marchant JS

Authors

Evgenii Chulkov Postdoctoral Fellow in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anthelmintics
Humans
Praziquantel
Schistosoma mansoni
Schistosomiasis mansoni
TRPM Cation Channels
Transient Receptor Potential Channels