Recent advances in the molecular mechanisms of human and animal models of myasthenia gravis.
The receptor-channel molecule is a dynamic system which exists in multiple conformations and that is the way we should think of it when we study antibody interaction with the molecule. The results presented here suggest that some antibodies may affect receptor function by occupying sites other than the receptor site. Some of these sites may by exposed only in certain conformations, and occupation of some site by antibodies may effect conformational changes. These small but perhaps important differences in cholinergic channel properties of the myasthenic muscle from the normal one are revealed by studying the effect of myasthenic sera on drug interactions with the channel sites. The sera of myasthenics are able to react with certain channel conformations and are able to affect the interaction of channel antagonists such as H12HTX and QNB. The sera appear to act preferentially with the open conformation of the channel. As a consequence of such an effect, important conformational changes of the channel may fail to occur upon activation.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006801:Humans; D007366:Intercostal Muscles / Q000378:metabolism / Q000503:physiopathology; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000032:analysis*
D002800:Cholinesterase Inhibitors; D007473:Ion Channels; D011950:Receptors, Cholinergic; D000109:Acetylcholine