HETEROGENEOUS LEVAMISOLE RECEPTORS - A SINGLE-CHANNEL STUDY OF NICOTINIC ACETYLCHOLINE-RECEPTORS FROM OESOPHAGOSTOMUM-DENTATUM

A muscle vesicle preparation from Oesophagostomum dentatum, a 5 mm par asitic nematode, was developed for single-channel recording. Propertie s of nicotinic acetylcholine receptors activated by the anthelmintic l evamisole (10 mu M) were investigated using cell-attached and isolated inside-out patches. The current-voltage relationships of the single-c hannel currents were linear with conductances in the range 24.6-57.7 p S (mean 39.5 pS). The distributions of open times were fitted with a s ingle exponential and mean open times were in the range 0.98-4.43 ms ( mean 2.2 ms). The distributions of conductances and open times of the channels showed that the receptors could not be described as a single homogeneous population. There were two main channel subtypes: one subt ype, designated G35, had a mean conductance of 35.2 pS and mean open t ime of 1.6 ms; another subtype, designated G45, had a mean conductance of 44.6 pS and mean open time of 2.7 ms. A channel with a conductance near 25 pS, designated G25, and a channel with a conductance near 55 pS, designated G55, were also observed. The designations were based on the mean conductances, G, of the channel subtypes. A model for the he terogeneous population of nicotinic acetylcholine channels predicting four subtypes of receptor separated by their conductance is discussed and related to the development of levamisole resistance. (C) 1997 Else vier Science B.V.