Injection of cDNA encoding the neuronal α7 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 α7 (WT α7) and the L247T α7 mutated nicotinic AcCho receptors (nAcChoRs). The receptors expressed were again blocked by α-bungarotoxin (100 nM) but exhibited both WT α7 and α7 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 α7 receptors, but exhibited a slow rate of desensitization and an I- V relation similar to those of α7 mutant receptors. Together, these findings indicate that the increased nAcChoR affinity and the decreased nAc- ChoR desensitization after Leu-247 mutation are uncoupled events. We propose that receptor diversity is predicted by permutations of WT α7 and L247T α7 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 α7 nAcChoRs.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 1997|
- nicotinic receptors
- Xenopus oocytes
ASJC Scopus subject areas