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MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans

Author

Listed:
  • Rajesh Ranganathan

    (Room 68-425, Massachusetts Institute of Technology)

  • Stephen C. Cannon

    (Harvard Medical School, Boston, Massachusetts 02115)

  • H. Robert Horvitz

    (Room 68-425, Massachusetts Institute of Technology)

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.

Suggested Citation

  • Rajesh Ranganathan & Stephen C. Cannon & H. Robert Horvitz, 2000. "MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans," Nature, Nature, vol. 408(6811), pages 470-475, November.
    • Handle: RePEc:nat:nature:v:408:y:2000:i:6811:d:10.1038_35044083
    DOI: 10.1038/35044083
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