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

Nature. 1993 Dec 2;366(6454):479-83. doi: 10.1038/366479a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Bungarotoxins / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Curare / pharmacology
  • Dihydro-beta-Erythroidine / pharmacology
  • Ion Channel Gating*
  • Molecular Sequence Data
  • Nicotine / pharmacology
  • Oocytes
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism*
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism*
  • Serotonin / pharmacology
  • Xenopus


  • Bungarotoxins
  • Receptors, Nicotinic
  • Receptors, Serotonin
  • Recombinant Fusion Proteins
  • Dihydro-beta-Erythroidine
  • Serotonin
  • Nicotine
  • Curare
  • Acetylcholine
  • Calcium