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Resistance to levamisole resolved at the single-channel level

^a Department of Preclinical Veterinary Sciences, R.(D.)S.V.S., Summerhall, University of Edinburgh, Edinburgh EH9 1QH, U.K.; and

^b Department of Pharmacology and Toxicology, Danish Centre For Experimental Parasitology, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark

Levamisole is commonly used to treat nematode parasite infections but therapy is limited by resistance. The purpose of this study was to determine the mechanism of resistance to this selective nicotinic drug. Levamisole receptor channel currents in muscle patches from levamisole-sensitive and levamisole-resistant isolates of the parasitic nematode Oesophagostomum dentatum were compared. The number of channels present in patches of sensitive and resistant isolates was similar at 10 µM levamisole, but at 30 µM and 100 µM the resistant isolate contained fewer active patches, suggesting desensitization. Mean P_o and open times were reduced in resistant isolates. The distribution of conductances of channels in the sensitive isolate revealed a heterogeneous receptor population and the presence of G25, G35, G40, and G45 subtypes. A G35 subtype was missing in the resistant isolate. Resistance to levamisole was produced by changes in the averaged properties of the levamisole receptor population, with some receptors from sensitive and resistant isolates having indistinguishable characteristics.—Robertson, A. P., Bjorn, H. E., Martin, R. J. Resistance to levamisole resolved at the single-channel level.

Key Words: Oesophagostomum dentatum • nAChR • patch • clamp • heterogeneity • subtypes

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