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摘要
'Embryonic' muscle-type nicotinic acetylcholine receptor channels (nAChRs) bind ligands at interfaces of - and - or -subunits. and sites differ in affinity, but their contributions to opening the channel have remained elusive. We compared high-resolution patch clamp currents evoked by epibatidine (Ebd), carbamylcholine (CCh) and acetylcholine (ACh). Ebd binds with 75-fold higher affinity at than at sites, whereas CCh and ACh prefer sites. Similar short (O1), intermediate (O2) and long (O3) types of opening were observed with all three agonists. O2 openings were maximally prevalent at low Ebd concentrations, binding at sites. By contrast, O1 openings appear to be generated at sites. In addition, two types of burst appeared: short bursts of an average of 0.75ms (B1) that should arise from the site, and long bursts of 12-25ms (B2) in duration arising from double liganded receptors. Limited by the temporal resolution, the closings within bursts were invariant at 3s. Corrected for missed closings, in the case of ACh the openings within long bursts lasted 170s and those in short bursts about 30s. Blocking sites with -conotoxin M1 (CTx) eliminated both O1 and B2 and left only O2 and the short B1 bursts, as expected. Furthermore we found desensitization when the receptors bound ACh only at the site. When CTx was applied to embryonic' mouse endplates, monoquantal current rise times were increased, and amplitude and decay time constants were reduced, as expected. Thus the and sites of nAChRs elicit specific channel-opening patterns.
- 出版日期2014-6-15
