Eur J Pharmacol 1999 Nov 03;3833:347-59. doi: 10.1016/s0014-2999(99)00646-9.

Agonist activation and alpha-bungarotoxin inhibition of wild type and mutant alpha7 nicotinic acetylcholine receptors.

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The properties of wild type and mutant rat nicotinic alpha7 receptors expressed in Xenopus oocytes were investigated using electrophysiology and site-directed mutagenesis. When compared at individual agonist concentrations, neither the normalised nicotinic, nor acetylcholine, responses of the wild type receptors were significantly different from the corresponding responses obtained from a first extracellular domain mutant, phenylalanine(189)tyrosine (P0.05). The dissociation constants (K(D)) of the wild type (4.7 nM) and Phe(189)Tyr mutant (5.2 nM) receptors for alpha-bungarotoxin were estimated by an electrophysiological approach. The similarity of the results suggests that the mutation did not lead to a widespread disruption of structure-function relationships, although a slight change in nicotine sensitivity may have occurred. In contrast, the mutations (Tyr(190)Gln, first extracellular domain), (Glu(261)Ala, M2 region) severely compromised receptor function. An additional mutation was made in a negatively charged motif of the second extracellular domain which is conserved in homomeric nicotinic receptors. This mutation, Asp(268)Ala, also caused a loss of function. Thus the structure-function relationships in nicotinic alpha7 receptors have parallels with heteromeric nicotinic receptors, but there may also be some marked differences.

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