Anthelmintic drug actions in resistant and susceptible C. elegans revealed by electrophysiological recordings in a multichannel microfluidic device

Publication date: Available online 30 October 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Janis C. Weeks, Kristin J. Robinson, Shawn R. Lockery, William M. RobertsAbstractMany anthelmintic drugs used to treat parasitic nematode infections target proteins that regulate electrical activity of neurons and muscles: ion channels (ICs) and neurotransmitter receptors (NTRs). Perturbation of IC/NTR function disrupts worm behavior and can lead to paralysis, starvation, immune attack and expulsion. Limitations of current anthelmintics include a limited spectrum of activity across species and the threat of drug resistance, highlighting the need for new drugs for human and veterinary medicine. Although ICs/NTRs are valuable anthelmintic targets, electrophysiological recordings are not commonly included in drug development pipelines. We designed a medium-throughput platform for recording electropharyngeograms (EPGs)—the electrical signals emitted by muscles and neurons of the pharynx during pharyngeal pumping (feeding)—in Caenorhabditis elegans and parasitic nematodes. The current study in C. elegans expands previous work in several ways. Detecting anthelmintic bioactivity in drugs, compounds or natural products requires robust, sustained pharyngeal pumping under baseline conditions. We generated concentration-response curves for stimulating pumping by perfusing 8-channel microfluidic devices (chips) with the neuromodulator serotonin, or wit...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research