Chimaeric nicotinic–serotonergic receptor combines distinct ligand binding and channel specificities

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Abstract
THE neuronal nicotinic α7 (nAChR) and 5-hydroxytryptamine (5HT3) receptors1–3 are ligand-gated ion channels with a homologous topological organization and have activation and desensitization reactions in common. Yet these homo-oligomeric receptors differ in the pharmacology of their binding sites for agonists and competitive antagonists3,4, and in their sensitivity to Ca2+ ions. The α7 channel is highly permeable to Ca2+ ions 5,6 and external Ca2+ ions potentiate, in an allosteric manner, the permeability response to acetylcholine, as shown for other neuronal nAChRs7,8. The 5HT3 channel, in contrast, is not permeable to Ca2+ ions, but blocked by them3,9. To assign these properties to delimited domains of the primary structure, we constructed several recombinant chimaeric α7–5HT3 receptors. We report here that one of the constructs expresses a functional receptor that contains the serotonergic channel still blocked by Ca2+ ions, but is activated by nicotinic ligands and potentiated by external Ca2+ ions.