Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans.
Sydney Brenner promoted Caenorhabditis elegans as a model organism, and subsequent investigations pursued resistance to the nicotinic anthelmintic drug levamisole in C. elegans at a genetic level. These studies have advanced our understanding of genes associated with neuromuscular transmission and resistance to the antinematodal drug. In lev-8 and lev-1 mutant C. elegans, levamisole resistance is associated with reductions in levamisole-activated whole muscle cell currents. Although lev-8 and lev-1 are known to code for nicotinic acetylcholine receptor (nAChR) subunits, an explanation for why these currents get smaller is not available. In wild-type adults, nAChRs aggregate at neuromuscular junctions and are not accessible for single-channel recording. Here we describe a use of LEV-10 knockouts, in which aggregation is lost, to make in situ recordings of nAChR channel currents. Our observations provide an explanation for levamisole resistance produced by LEV-8 and LEV-1 mutants at the single-channel level.
Qian
Hai
H
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
Robertson
Alan P
AP
Powell-Coffman
Jo Anne
JA
Martin
Richard J
RJ
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004351:Drug Resistance; D007473:Ion Channels / Q000502:physiology*; D007978:Levamisole / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics*; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; C492294:LEV-10 protein, C elegans; C531559:Lev-1 protein, C elegans; C531558:Lev-8 protein, C elegans; D008565:Membrane Proteins; D011978:Receptors, Nicotinic; D007978:Levamisole