Characterization of the Ca2 -Gated and Voltage-Dependent K -Channel Slo-1 of Nematodes and Its Interaction with Emodepside
Daniel Kulke, Georg von Samson-Himmelstjerna, Sandra M Miltsch, Adrian J Wolstenholme, Aaron R Jex, Robin B Gasser, Cristina Ballesteros, Timothy G Geary, Jennifer Keiser, Simon Townson, Achim Harder, Juergen Kruecken
PLoS Neglected Tropical Diseases | PUBLIC LIBRARY SCIENCE | Published : 2014
The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and relate..View full abstract
The present study was performed as a collaborative Research project between Bayer HealthCare and the Institute of Parasitology and Tropical Veterinary Medicine, Freie Universitat Berlin. Accordingly, the Institute of Parasitology and Tropical Veterinary Medicine, Freie Universitat Berlin received a Project specific research grant from Bayer HealthCare AG. The funders, except for AH and DK, had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.