Abstract
THE neurohormone 5-hydroxytryptamine (5HT or serotonin) exerts its effects by binding to several distinct receptors1. One of these is the M-receptor of Gaddum and Picarelli2, now called the 5-HT3 receptor, through which 5-HT acts to excite enteric neurons. Ligand-binding and functional studies have shown that the 5-HT3 receptor is widely distributed in peripheral and central nervous tissue3–5 and evidence suggests that the receptor might incorporate an ion channel permeable to cations6,7. We now report the first recordings of currents through single ion channels activated by 5-HT3 receptors, in excised (outside-out) membrane patches from neurons of the guinea pig submucous plexus. Whereas application of acetylcholine activated predominantly a 40-pS channel, 5-HT caused unitary currents apparently through two channels of conductances of 15 and 9 pS, which were reversibly blocked by antagonists of the 5-HT3 receptor. Receptors for amine neurotransmitters, including 5-HT1, and 5-HT2, have previously been thought to transduce their effects through GTP-binding proteins1: the direct demonstration that 5-HT3 receptors are ligand-gated ion channels implies a role for 5-HT, and perhaps other amines, as a 'fast' synaptic transmitter.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Peroutka, S. J. Trends Neurosci. 11, 496–500 (1988).
Gaddum, J. H. & Picarelli, Z. P. Br. J. Pharmacol. 12, 323–328 (1957).
Richardson, B. P., Engel, G., Donatsch, P. & Stadler, P. A. Nature 316, 126–131 (1985).
Richardson, B. P. & Engel, G. Trends Neurosci. 9, 424–428 (1986).
Kilpatrick, G. J., Jones, B. J. & Tyers, M. B. Nature 330, 746–748 (1987).
Surprenant, A. & Crist, J. Neuroscience 24, 283–295 (1988).
Yakel, J. L. & Jackson, M. B. Neuron 1, 615–621 (1988).
Nield, T. O. Gen. Pharmacol. 12, 281–284 (1978).
Higashi, H. & Nishi, S. J. Physiol. 323, 543–567 (1982).
Mawe, G. M., Branchek, T. A. & Gershon, M. D. Proc. natn. Acad. Sci. U.S.A. 83, 9799–9803 (1986).
Skok, V. I. & Selyanko, A. A. in Integrative Functions of the Autonomic Nervous System (eds Brooks, C. McC., Koizumi, K. & Sato, A.) 248–253 (Elsevier, Amsterdam, 1979).
Surprenant, A. & North, R. A. Proc. R. Soc. Lond. B. 234, 85–114 (1988).
North, R. A., Surprenant, A. & Tatsumi, H. J. Physiol. 406, 179P.*
Stroud, R. M. & Finer-Moore, J. A. Rev. Cell Biol. 1, 317–351 (1985).
Steinbach, J. H. & Ifune, C. Trends Neurosci. 11, 3–6 (1989).
Derkach, V. A., North, R. A., Selyanko, A. A. & Skok, V. I. J. Physiol. 388, 141–152 (1987).
Colquhoun, D., Ogden, D. C. & Mathie, A. Trends Pharmacol. Sci. 8, 465–472 (1987).
Cull-Candy, S. G., Howe, J. R. & Ogden, D. C. J. Physiol. 400, 189–222 (1988).
Schofield, P. R. et al. Nature 328, 221–227 (1987).
Grenningloh, G. et al. Nature 328, 215–220 (1987).
Paton, W. D. M. & Zaimis, E. J. Br. J. Pharmacol. 6, 155–168 (1951).
Lipscombe, D. & Rang, H. P. J. Neurosci. 8, 3258–3265 (1988).
Nathanson, N. A. Rev. Neurosci. 10, 195–236 (1987).
Bormann, J. Trends Neurosci. 11, 112–116 (1988).
Sugiyama, H., Ito, I. & Hirono, C. Nature 325, 531–533 (1987).
Sladeczek, F., Recasens, M. & Bockaert, J. Trends Neurosci. 11, 545–549 (1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Derkach, V., Surprenant, A. & North, R. 5-HT3 receptors are membrane ion channels. Nature 339, 706–709 (1989). https://doi.org/10.1038/339706a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/339706a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.