Heterogeneous levamisole receptors: a single-channel study of nicotinic acetylcholine receptors from Oesophagostomum dentatum.
A muscle vesicle preparation from Oesophagostomum dentatum, a 5 mm parasitic nematode, was developed for single-channel recording. Properties of nicotinic acetylcholine receptors activated by the anthelmintic levamisole (10 microM) were investigated using cell-attached and isolated inside-out patches. The current-voltage relationships of the single-channel currents were linear with conductances in the range 24.6-57.7 pS (mean 39.5 pS). The distributions of open times were fitted with a single 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 subtype, designated G35, had a mean conductance of 35.2 pS and mean open time 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 heterogeneous population of nicotinic acetylcholine channels predicting four subtypes of receptor separated by their conductance is discussed and related to the development of levamisole resistance.
Martin
R J
RJ
Department of Preclinical Veterinary Sciences, R(D.)S.V.S. Summerhall, University of Edinburgh, UK. R.J.Martin@ed.ac.uk
Robertson
A P
AP
Bjorn
H
H
Sangster
N C
NC
D000818:Animals; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects; D007978:Levamisole / Q000378:metabolism* / Q000494:pharmacology; D009815:Oesophagostomum / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011955:Receptors, Drug / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000502:physiology*
D007473:Ion Channels; D011955:Receptors, Drug; D011978:Receptors, Nicotinic; D007978:Levamisole