The selectivity of the channel coupled to the 5-HT3 receptor

Brain Res. 1990 Nov 12;533(1):46-52. doi: 10.1016/0006-8993(90)91793-g.


The 5-HT3 receptor is unusual among receptors for biogenic amines in that it is directly coupled to an ion channel that is highly permeable to Na+ and K+. We have studied the permeation properties of this channel in order to achieve a more detailed understanding of its physiological function and to extend the comparison with other ligand gated channels. The 5-HT3 receptor channel is significantly permeable to the organic cations Tris, choline, and N-methyl-glucamine, with permeabilities decreasing with size. The permeability ratios for Tris and choline are similar to those determined for the nicotinic receptor; the permeability ratio for Tris is also similar to that of a non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptor. This suggests that the diameters at the narrowest parts of these 3 channels are similar. The Ca2+ permeability of the 5-HT3 receptor channel is relatively low, with an upper bound to PCa/PNa estimated as 0.076. The single channel conductance, as determined by noise analysis, was also relatively low, with a value of 4.4 +/- 0.5 pS. Thus, both the Ca2+ permeability and single channel conductance are lower than those of the nicotinic receptor. In these respects, the 5-HT3 receptor is closer to non-NMDA excitatory amino acid receptors. These results are interpreted in terms of a model of the 5-HT3 receptor channel in which the interior has a lower polarizability, and possibly a greater length, in comparison with the nicotinic acetylcholine receptor channel.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cations, Divalent / pharmacology
  • Chlorides / metabolism
  • Ion Channels / physiology*
  • Membrane Potentials / drug effects
  • Permeability
  • Potassium / metabolism
  • Receptors, Nicotinic / physiology
  • Receptors, Serotonin / physiology*
  • Sodium / metabolism
  • Structure-Activity Relationship


  • Cations, Divalent
  • Chlorides
  • Ion Channels
  • Receptors, Nicotinic
  • Receptors, Serotonin
  • Sodium
  • Potassium