Amino Acids

, Volume 17, Issue 3, pp 243–255 | Cite as

Ion permeation properties of a cloned human 5-HT3 receptor transiently expressed in HEK 293 cells

  • Shinobu Mochizuki
  • A. Miyake
  • K. Furuichi
Full Papers


Human 5-HT3 receptors expressed in HEK 293 cells were studied using patch-clamp techniques. The permeability ratios of cations to Na+ were Li+, 1.16; K+, 1.04; Rb+, 1.11; Cs+ 1.11; NMDG+, 0.04; Ca2+, 0.49, and Mg2+, 0.37. The permeability sequence of the alkali metal cations was Li+ > Rb+ = Cs+ > K+ > Na+. Increased external concentrations of Ca2+ or Mg2+ decreased 5-HT-induced currents at all potentials tested in a voltage-independent manner. The single-channel conductance of human 5-HT3 receptors measured by fluctuation analysis of whole-cell currents was 790 ± 100fS. Differences in the basic properties of 5-HT3 receptors between species may explain interspecies differences in pharmacological properties.


Amino acids Serotonin receptor Serotonin-3 receptor Ion channel Ion permeability 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alhaider AA (1997) Effect of systemically administered SR 57227A on the tail-flick latency in mice. Pharmacologist 39: 108Google Scholar
  2. Anderson CR, Stevens CF (1973) Voltage-clamp analysis of acetylcholine produced endplate current fluctuations at the frog neuromuscular junction. J Physiol 235: 655–691PubMedGoogle Scholar
  3. Ascher P, Nowak L (1988) The role of divalent cations in theN-methyl-d-aspartate responses of mouse central neurones in culture. J Physiol 399: 247–266PubMedGoogle Scholar
  4. Belelli D, Balcarek JM, Hope AG, Peters JA, Lambert JJ, Blackburn TP (1995) Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. Mol Pharmacol 48: 1054–1062PubMedGoogle Scholar
  5. Brown AM, Hope AG, Lambert JJ, Peters JA (1998) Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). J Physiol 507: 653–665PubMedGoogle Scholar
  6. Bunce K, Tyers M, Beranek P (1991) Clinical evaluation of 5-HT3 receptor antagonists as anti-emetics. Trends Pharmacol Sci 12: 46–48PubMedGoogle Scholar
  7. Butler A, Elswood CJ, Burridge J, Ireland SJ, Bunce KT, Kilpatrick GJ, Tyers MB (1990) The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues. Br J Pharmacol 101: 591–598PubMedGoogle Scholar
  8. Chen C, Okayama H (1987) High efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7: 2745–2752PubMedGoogle Scholar
  9. Derkach V, Surprenant A, North RA (1989) 5-HT3 receptors are membrane ion channels. Nature 339: 706–709PubMedGoogle Scholar
  10. Gill CH, Peters JA, Lambert JJ (1995) An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK293 cells. Br J Pharmacol 114: 1211–1221PubMedGoogle Scholar
  11. Greenshaw AJ (1993) Behavioural pharmacology of 5-HT3 receptor antagonists: a critical update on therapeutic potential. Trends Pharmacol Sci 14: 265–270PubMedGoogle Scholar
  12. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391: 85–100Google Scholar
  13. Higashi H, Nishi S (1982) 5-Hydroxytryptamine receptors of visceral primary afferent neurones on rabbit nodose ganglia. J Physiol 323: 543–567PubMedGoogle Scholar
  14. Hill B (1992) Ion channels of excitable membranes, 2nd edn. Sinauer Associates Inc., Sunderland, pp 288–290Google Scholar
  15. Hodgkin AL (1951) The ionic basis of electrical activity in nerve and muscle. Biol Rev 26: 339–409Google Scholar
  16. Hope AG, Downie DL, Sutherland L, Lambert JJ, Peters JA, Burchell B (1993) Cloning and functional expression of an apparent splice variant of the murine 5-HT3 receptor A subunit. Fur J Pharmacol 245: 187–192Google Scholar
  17. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994) International union of pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46: 157–203PubMedGoogle Scholar
  18. Hussy N, Lukas W, Jones KA (1994) Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparsion with native mouse receptors. J Physiol 481: 311–323PubMedGoogle Scholar
  19. Ireland SJ, Tyers MB (1987) Pharmacological characterization of 5-hydroxytryptamineinduced depolarization of the rat isolated vagus nerve. Br J Pharmacol 90: 229–238PubMedGoogle Scholar
  20. Isenberg KE, Ukhum IA, Holstad SG, Jafri S, Uchida U, Zorumski CF, Yang J (1993) Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit. NeuroReport 5: 121–124PubMedGoogle Scholar
  21. Kamato T, Ito H, Nagakura Y, Nishida A, Yuki H, Yamano M, Miyata K (1993) Mechanisms of cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets. Eur J Pharmacol 238: 369–376PubMedGoogle Scholar
  22. Lambert JJ, Peters JA, Hales TG, Dempster J (1989) The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques. Br J Pharmacol 97: 27–40PubMedGoogle Scholar
  23. Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D (1991) Primary structure and functional expression of the 5-HT3 receptor, a serotonin-gated ion channel. Science 254: 432–437PubMedGoogle Scholar
  24. Marshall J, Molloy R, Moss GWJ, Howe JR, Hughes TE (1995) The jellyfish green fluorescent protein: a new tool for studying ion channel expression and function. Neuron 14: 211–215Google Scholar
  25. Miyake A, Mochizuki S, Takemoto Y, Akuzawa S (1995) Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol 48: 407–416PubMedGoogle Scholar
  26. Peters JA, Hales TG, Lambert JJ (1988) Divalent cations modulate 5-HT3 receptorinduced currents in N1E-115 neuroblastoma cells. Eur J Pharmacol 151: 491–495PubMedGoogle Scholar
  27. Peters JA, Malone HM, Lambert JJ (1992) Recent advances in the electrophysiological characterization of 5-HT3 receptors. Trends Pharmacol Sci 13: 391–397PubMedGoogle Scholar
  28. Peters JA, Malone HM, Lambert JJ (1993) An electrophysiological investigation of the properties of 5-HT3 receptors of rabbit nodose ganglion neurones in culture. Br J Pharmacol 110: 665–676PubMedGoogle Scholar
  29. Poncelet M, Perio A, Simiand J, Gout G, Soubrie P, Le Fur G (1995) Antidepressant-like effects of SR 57227A, a 5-HT3 receptor agonist, in rodents. J Neural Transm 102: 83–90Google Scholar
  30. Reuter H, Stevens CF (1980) Ion conductance and ion selectivity of potassium channels in snail neurons. J Membr Biol 57: 103–118PubMedGoogle Scholar
  31. Robinson RA, Stokes RH (1959) Electrolyte solutions, 2nd edn. Butterworths, London, pp 230–237Google Scholar
  32. Werner P, Kawashima E, Reid J, Hussy N, Lundström K, Buell G, Humbert Y, Jones KA (1994) Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Mol Brain Res 26: 233–241PubMedGoogle Scholar
  33. Yakel JL, Jackson MB (1988) 5-HT3 receptors mediated rapid responses in cultured hippocampus and a clonal cell line. Neuron 1: 615–621PubMedGoogle Scholar
  34. Yakel JL, Shao XM, Jackson MB (1990) The selectivity of the channel coupled to the 5-HT3 receptor. Brain Res 533: 46–52PubMedGoogle Scholar
  35. Yang J (1990) Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. J Gen Physiol 96: 1177–1198PubMedGoogle Scholar
  36. Yang J, Mathie A, Hille B (1992) 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons. J Physiol 448: 237–256PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • Shinobu Mochizuki
    • 1
  • A. Miyake
    • 1
  • K. Furuichi
    • 1
  1. 1.Molecular Medicine Laboratories, Institute for Drug Discovery ResearchYamanouchi Pharmaceutical Co., Ltd.IbarakiJapan

Personalised recommendations