Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities.
The neuronal nicotinic alpha 7 (nAChR) and 5-hydroxytryptamine (5HT3) receptors 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 antagonists, and in their sensitivity to Ca2+ ions. The alpha 7 channel is highly permeable to Ca2+ ions and external Ca2+ ions potentiate, in an allosteric manner, the permeability response to acetylcholine, as shown for other neuronal nAChRs. The 5HT3 channel, in contrast, is not permeable to Ca2+ ions, but blocked by them. To assign these properties to delimited domains of the primary structure, we constructed several recombinant chimaeric alpha 7-5HT3 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.
Eiselé
J L
JL
Unité de Recherche Associée au Centre National de la Recherche Scientifique D1284, Institut Pasteur, Paris, France.
Bertrand
S
S
Galzi
J L
JL
Devillers-Thiéry
A
A
Changeux
J P
JP
Bertrand
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003472:Curare / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009538:Nicotine / Q000494:pharmacology; D009865:Oocytes; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014981:Xenopus
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D011993:Recombinant Fusion Proteins; D004079:Dihydro-beta-Erythroidine; D012701:Serotonin; D009538:Nicotine; D003472:Curare; D000109:Acetylcholine; D002118:Calcium