The Anthelmintic Agent Oxantel is a Partial Agonist of C. elegans Muscle Levamisole-Sensitive Nicotinic Receptor

BERGÉ IGNACIO; RAYES DIEGO; BOUZAT CECILIA

Huerta Grande, Córdoba

Congreso; Second Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neurosciences (TAN).; 2010

Sociedad Argentina de Investigación en Neurociencias (SAN)

The availability of a sequenced genome with 60% of the genes having vertebrate counterparts has led to the adoption of C. elegans as a model of neuronal diseases and is used in drug screenings. C. elegans expresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) and nicotine-sensitive (N-AChR). Using a primary culture method that allows in vitro differentiation of embryonic cells into muscle cells, we explore activation of C. elegans AChRs by the nematocide drug oxantel. Patch-clamp recordings showed that oxantel elicits single-channel openings of ~3.7 pA at -100 mV, similar to those of levamisole-activated nAChRs, indicating that activity corresponds to L-AChRs. Oxantel-activated channels are 2- and 3.7-fold briefer compared to ACh and levamisole respectively, and the opening frequency is 20-fold lower than that of ACh-activated channels. Macroscopic responses elicited by oxantel are <1 % of those elicited by ACh. Oxantel (5 mM) does not alter worm locomotion whereas 100-fold lower concentrations of levamisole significantly inhibit locomotion.  We conclude that oxantel is a partial agonist of muscle L-AChRs. These results contribute to the characterization of the pharmacology related to neuromuscular transmission in the model organism