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Publication Abstract from PubMed

Nicotinic acetylcholine receptors (nAChRs) are targets of general anesthetics, but functional sensitivity to anesthetic inhibition varies dramatically among different subtypes of nAChRs. Potential causes underlying different functional responses to anesthetics remain elusive. Here we show that in contrast to the alpha7 nAChR, the alpha7beta2 nAChR is highly susceptible to inhibition by the volatile anesthetic isoflurane in electrophysiology measurements. Isoflurane-binding sites in beta2 and alpha7 were found at the extracellular and intracellular end of their respective transmembrane domains using NMR. Functional relevance of the identified beta2 site was validated via point mutations and subsequent functional measurements. Consistent with their functional responses to isoflurane, beta2 but not alpha7 showed pronounced dynamics changes, particularly for the channel gate residue Leu-249(9'). These results suggest that anesthetic binding alone is not sufficient to generate functional impact; only those sites that can modulate channel dynamics upon anesthetic binding will produce functional effects.

Insights into distinct modulation of alpha7 and alpha7beta2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.,Mowrey DD, Liu Q, Bondarenko V, Chen Q, Seyoum E, Xu Y, Wu J, Tang P J Biol Chem. 2013 Dec 13;288(50):35793-800. doi: 10.1074/jbc.M113.508333. Epub, 2013 Nov 5. PMID:24194515^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.