Electrophysiological investigation of anthelmintic resistance.
It is pointed out that two of the three major groups of anthelmintic act by opening membrane ion-channels. It is appropriate, therefore, to use electrophysiological methods to study the properties of the sites of action of these drugs and the changes in the properties of these receptor sites associated with resistance. This paper describes the use of the patch-clamp technique to observe the currents that flow through the levamisole-activated channels as they open and close in levamisole-sensitive and levamisole-resistant isolates. It was found that, on average, the proportion of time the channels are open, is less in the resistant isolate. The patch-clamp technique also showed that the ion-channels are heterogeneous and that one of the subtypes is lost with the appearance of resistance. The use of the current clamp technique is illustrated to record a site of action of ivermectin in the pharyngeal muscle of Ascaris.
Martin
R J
RJ
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames 50011, USA. rjmartin@iastate.edu
Robertson
A P
AP
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001200:Ascaris / Q000187:drug effects; D004351:Drug Resistance; D004594:Electrophysiology; D007473:Ion Channels / Q000502:physiology*; D007559:Ivermectin / Q000494:pharmacology; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects; D009815:Oesophagostomum / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000662:veterinary
D000871:Anthelmintics; D007473:Ion Channels; D007559:Ivermectin