National Academy of Sciences, Proceedings of the National Academy of Sciences, 4(94), p. 1539-1543, 1997
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Injection of cDNA encoding the neuronal α 7 subunit into Xenopus oocytes yields homomeric receptors showing responses to AcCho that have low affinity, fast desensitization, nonlinear current–voltage ( I–V ) relation, and sensitivity to α-bungarotoxin (α-BTX) and 5-hydroxytryptamine (5HT), both substances acting as antagonists. Mutation of the Leu-247, located in the channel domain, changes 5HT from an antagonist to an agonist, slows the rate of desensitization, renders the I–V relation linear, and increases the affinity for acetylcholine (AcCho). A study was made of receptors expressed after injecting Xenopus oocytes with mixtures of cDNAs encoding the wild-type α 7 (WT α 7 ) and the L247T α 7 mutated nicotinic AcCho receptors (nAcChoRs). The receptors expressed were again blocked by α-bungarotoxin (100 nM) but exhibited both WT α 7 and α 7 mutant functional characteristics. Out of eight different types of hybrid receptors identified, most were inhibited by 5HT (1 mM) and showed low sensitivity to AcCho, like the WT α 7 receptors, but exhibited a slow rate of desensitization and an I–V relation similar to those of α 7 mutant receptors. Together, these findings indicate that the increased nAcChoR affinity and the decreased nAcChoR desensitization after Leu-247 mutation are uncoupled events. We propose that receptor diversity is predicted by permutations of WT α 7 and L247T α 7 subunits in a pentameric symmetrical model and that even partial replacement of Leu-247 with a polar residue within the leucine ring in the channel domain considerably influences the properties of neuronal α 7 nAcChoRs.