Mod-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in c.  elegans

ABSTRACT The neurotransmitter and neuromodulator serotonin (5-HT) functions by binding either to metabotropic G-protein-coupled receptors (for example, 5-HT1, 5-HT2, 5-HT4 to 5-HT7), which

mediate ‘slow’ modulatory responses through numerous second messenger pathways1, or to the ionotropic 5-HT3 receptor, a non-selective cation channel that mediates ‘fast’ membrane

depolarizations2. Here we report that the gene _mod-1_ (for modulation of locomotion defective) from the nematode _Caenorhabditis elegans_ encodes a new type of ionotropic 5-HT receptor, a

5-HT-gated chloride channel. The predicted MOD-1 protein is similar to members of the nicotinic acetylcholine receptor family of ligand-gated ion channels, in particular to GABA

(γ-aminobutyric acid)- and glycine-gated chloride channels. The MOD-1 channel has distinctive ion selectivity and pharmacological properties. The reversal potential of the MOD-1 channel is

dependent on the concentration of chloride ions but not of cations. The MOD-1 channel is not blocked by calcium ions or 5-HT3a-specific antagonists but is inhibited by the metabotropic 5-HT

receptor antagonists mianserin and methiothepin. _mod-1_ mutant animals are defective in a 5-HT-mediated experience-dependent behaviour3 and are resistant to exogenous 5-HT, confirming that

MOD-1 functions as a 5-HT receptor _ in vivo_. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

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_J. Gen. Physiol. _ 107, 559–576 ( 1996). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank N. Buttner, D. Omura and P. Reddien for suggestions concerning

this manuscript; G. Moulder and R. Barstead for help in isolating the _ mod-1(ok103)_ allele; L. Liu and C. Johnson for sharing the _ mod-1(nr2043)_ allele before publication; and D. Julius

for the 5-HT3a cDNA clone. This work was supported by a grant from the United States Public Health Service (H.R.H.). R.R. is supported by a Howard Hughes Medical Institute predoctoral

fellowship. H.R.H. is an Investigator of the Howard Hughes Medical Institute. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Howard Hughes Medical Institute Department of Biology, Room

68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA Rajesh Ranganathan & H. Robert Horvitz * Department of Neurobiology, and

Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, Boston, 02114, Massachusetts , USA Stephen C. Cannon Authors * Rajesh Ranganathan

View author publications You can also search for this author inPubMed Google Scholar * Stephen C. Cannon View author publications You can also search for this author inPubMed Google Scholar

* H. Robert Horvitz View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to H. Robert Horvitz. SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ranganathan, R., Cannon, S. & Horvitz, H. MOD-1 is a serotonin-gated

chloride channel that modulates locomotory behaviour in _C. elegans_. _Nature_ 408, 470–475 (2000). https://doi.org/10.1038/35044083 Download citation * Received: 28 July 2000 * Accepted: 11

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