Single-channel properties of N- and L-subtypes of acetylcholine receptor in Ascaris suum.
We are interested in the properties of the target site of cholinergic anti-nematodal drugs for therapeutic reasons. The target receptors are ligand-gated ion channels that have different subtypes, and each subtype may have a different pharmacology. In a contraction assay using the parasitic nematode Ascaris suum, our laboratory has identified several subtypes, including an N-subtype, preferentially activated by nicotine, and an L-subtype, preferentially activated by levamisole. Here we use patch-clamp recordings to test the hypothesis that the single-channel selectivities of nicotine and levamisole are different. Unitary currents evoked by nicotine in this preparation were characterised for the first time. In some patches, both nicotine and levamisole activated small- and large-conductance channels. In other patches, the agonists activated just one channel amplitude. Discriminant analysis allowed classification of the one-conductance patch channels into the small or large categories, based on sets defined by the two-conductance patch data. The small channels had a conductance of 26.1+/-1.5 pS, n=18 (mean+/-SEM); the large conductance channels had a conductance of 38.8+/-1.2 pS, n=23 (mean+/-SEM). Analysis of amplitude histograms of the two-conductance patches showed that nicotine preferentially activated the small-conductance channels and levamisole preferentially activated the large-conductance channels. Our observations suggest that the N-subtype receptor channel has a conductance of 26 pS channel and the L-subtype receptor channel has a conductance of 39 pS.
Levandoski
Mark M
MM
Department of Chemistry, Grinnell College, Grinnell, IA 50112, USA.
Robertson
Alan P
AP
Kuiper
Shonda
S
Qian
Hia
H
Martin
Richard J
RJ
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D017165:Ascaris suum / Q000378:metabolism*; D016002:Discriminant Analysis; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007978:Levamisole / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000871:Anthelmintics; D007473:Ion Channels; D018722:Nicotinic Agonists; D011950:Receptors, Cholinergic; D007978:Levamisole; D009538:Nicotine