CHIMERIC NICOTINIC SEROTONERGIC RECEPTOR COMBINES DISTINCT LIGAND-BINDING AND CHANNEL SPECIFICITIES

THE neuronal nicotinic alpha7 (nAChR) and 5-hydroxytryptamine (5HT3) r eceptors1-3 are ligand-gated ion channels with a homologous topologica l organization and have activation and desensitization reactions in co mmon. Yet these homo-oligomeric receptors differ in the pharmacology o f their binding sites for agonists and competitive antagonists3,4, and in their sensitivity to Ca2+ ions. The alpha7 channel is highly perme able to Ca2+ ions5,6 and external Ca2+ ions potentiate, in an alloster ic manner, the permeability response to acetylcholine, as shown for ot her neuronal nAChRs7,8. The 5HT3 channel, in contrast, is not permeabl e to Ca2+ ions, but blocked by them3,9. To assign these properties to delimited domains of the primary structure, we constructed several rec ombinant chimaeric alpha7-5HT3 receptors. We report here that one of t he constructs expresses a functional receptor that contains the seroto nergic channel still blocked by Ca2+ ions, but is activated by nicotin ic ligands and potentiated by external Ca2+ ions.