Elsevier

Neuropharmacology

Volume 39, Issue 13, December 2000, Pages 2570-2590
Neuropharmacology

Human α6 AChR subtypes: subunit composition, assembly, and pharmacological responses

https://doi.org/10.1016/S0028-3908(00)00144-1Get rights and content
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Abstract

Many nicotinic acetylcholine receptor (AChR) subunits are known to be co-expressed with the α6 subunit in neurons. Because α6β4 AChRs assemble inefficiently and α6β2 AChRs not at all, more complex mixtures of human subunit cDNAs were tested for their abilities to form functional AChRs when expressed in Xenopus oocytes. α6β4β3 AChRs produced the largest and most consistent responses. α6α3β2 AChRs exhibited reduced potency for ACh and increased potency and efficacy for nicotine compared to α3β2 AChRs, but similar resistance to functional inactivation after prolonged exposure to nicotine. α6α4β2 AChRs differed little in potency or efficacy for ACh or nicotine compared to α4β2 AChRs, and had similarly high sensitivity to inactivation by prolonged exposure to nicotine. Co-expression of α6 and β2 cRNAs resulted in large numbers of 3H-epibatidine binding sites in the form of large aggregates but not in functional pentameric AChRs. Co-expression of α6, β2, and α5 resulted in assembly of some functional pentameric AChRs. Chimeras with the large extracellular domain of α6 and the rest from either α3 or α4 efficiently formed functional AChRs. Thus, the extracellular domain of α6 efficiently assembles with β2 to form ACh binding sites, but more C-terminal domains cause difficulties in forming pentameric AChRs. Chimeric α6/α3 and α6/α4 AChRs containing either β2 or β4 subunits were blocked by α-conotoxin MII which had previously been reported to be specific for α3β2 AChRs.

Keywords

Acetylcholine receptors
Nicotinic receptors
α6 Subunits
Nicotine

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