title: Inhibition of Schistosoma mansoni ether-a-go-go related gene-encoded potassium channels leads to hypermotility and impaired egg production.
abstract: The purpose of this work was to investigate the effect of ether-a-go-go related gene (ERG) potassium channel inhibition on Schistosoma mansoni. Use of dofetilide to block the schistosome ERGs resulted in a striking 'corkscrew' effect. The worms were unable to control their motility; they were hypermotile. The treated worms produced abnormal eggs, some of which consisted of little more than a spine. One of the S. mansoni ERGs (SmERGs), Smp_161140, was chosen for further study by RNAi. The transcript was knocked down to 50% compared to the controls. These RNAi-treated worms demonstrated seizure-like movements. In S. mansoni, as in other organisms, ERG channels seem to play a role in regulating muscle excitability. This work shows that egg production can be greatly reduced by effectively targeting muscle coordination in these important parasites.
authors.affiliation: Institute of Parasitology, Justus-Liebig-University Giessen, Germany. Electronic address: sophie_manuel@yahoo.co.uk.
authors.forename: S J
authors.initials: SJ
authors.lastname: Parker-Manuel
authors.affiliation: Institute of Parasitology, Justus-Liebig-University Giessen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hahnel
authors.affiliation: Institute of Parasitology, Justus-Liebig-University Giessen, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Grevelding
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001700:Biomphalaria; D006224:Cricetinae; D018076:DNA, Complementary / Q000737:chemistry; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008647:Mesocricetus; D009068:Movement / Q000187:drug effects / Q000502:physiology; D010058:Oviposition / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D051638:Ether-A-Go-Go Potassium Channels; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide
keywords: Dofetilide; Egg production; Ether-a-go-go related gene; Hypermotility; Schistosoma mansoni; Voltage-gated potassium channel