Acetylcholine receptors of human skeletal muscle: a species difference detected by snake neurotoxins.
The binding abilities of the nicotinic acetylcholine receptors (AChRs) of the skeletal muscles of man and other vertebrates to two typical curaremimetic toxins, erabutoxin b (Eb) and alpha-bungarotoxin (alpha-BT), were investigated. Fluorescent microscopy using rhodamine-labeled erabutoxin b (TMR-Eb) and FITC-labeled alpha-bungarotoxin (FITC-alpha-BT) revealed that AChRs of human and chimpanzee muscles were stained with FITC-alpha-BT, but not with TMR-Eb. In contrast, the AChRs of mouse muscle were stained with both fluorescent toxins. The stainings of human and chimpanzee AChRs with FITC-alpha-BT were inhibited by preincubation with unmodified alpha-BT, but not with either unmodified Eb or other short-chain neurotoxins. Binding experiments using 125I-labeled Eb ([125I]Eb) and 125I-labeled alpha-BT ([125I]alpha-BT) showed that the affinity of human AChRs for [125I]Eb was unusually low. Electrophysiological experiments showed that both acetylcholine potential and end-plate potential of human muscle were blocked by addition of alpha-BT, but not by Eb. On the contrary, acetylcholine potential of rat muscle was blocked by addition of Eb. All these results indicate that AChRs of human and chimpanzee muscles are different from those of other animals in having an exceptionally low affinity for Eb and other short-chain neurotoxins. The results suggest a heterogeneity among vertebrate AChRs concerning their reactivities to curaremimetic toxins.
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism; D004870:Erabutoxins / Q000378:metabolism; D006801:Humans; D007366:Intercostal Muscles / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D002679:Pan troglodytes; D011898:Ranidae; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013045:Species Specificity
D002038:Bungarotoxins; D009498:Neurotoxins; D011950:Receptors, Cholinergic; D004870:Erabutoxins; C032917:erabutoxin b