Tunicamycin increases desensitization of junctional and extrajunctional acetylcholine receptors expressed in Xenopus oocytes by a mechanism independent of N-glycosylation blocking.
Extrajunctional and junctional mouse muscle acetylcholine receptors (AChRs) expressed in Xenopus oocytes in the presence of tunicamycin desensitized more rapidly than the corresponding AChRs synthesized in the absence of tunicamycin. The two types of AChR expressed in non-tunicamycin-treated oocytes could be distinguished by their different rates of desensitization, but tunicamycin diminished this difference. The effect of tunicamycin on the AChR desensitization appeared to be reversible, and coapplication of tunicamycin with acetylcholine (ACh) also caused a similar effect on desensitization of these AChRs suggesting that the effect of tunicamycin was mediated by a mechanism independent of N-glycosylation blocking. In addition, tunicamycin increased the amplitude of membrane current elicited by application of lower doses of ACh and accelerated the rate of desensitization, which suggests that tunicamycin favors an open channel state and, therefore, accelerates transition towards a desensitized state. Tunicamycin also increased the membrane current decay elicited by ACh in oocytes expressing incomplete AChRs, missing the beta, gamma, epsilon, or delta subunits.
Nishizaki
T
T
Department of Psychobiology, University of California, Irvine 92717-4550.
Sumikawa
K
K
D000818:Animals; D002478:Cells, Cultured; D004247:DNA; D006031:Glycosylation / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials; D009132:Muscles / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D010063:Ovum; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014415:Tunicamycin / Q000494:pharmacology*; D014981:Xenopus
D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D014415:Tunicamycin; D004247:DNA