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

Nature. 2000 Nov 23;408(6811):470-5. doi: 10.1038/35044083.

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 pathways, or to the ionotropic 5-HT3 receptor, a non-selective cation channel that mediates 'fast' membrane depolarizations. 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 (gamma-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 behaviour and are resistant to exogenous 5-HT, confirming that MOD-1 functions as a 5-HT receptor in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Cell Line
  • Chloride Channels / genetics
  • Chloride Channels / physiology*
  • Exons
  • Genes, Helminth
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology
  • Humans
  • Introns
  • Ion Channel Gating
  • Molecular Sequence Data
  • Mutation
  • Patch-Clamp Techniques
  • Serotonin / physiology*
  • Transfection
  • Xenopus laevis

Substances

  • Caenorhabditis elegans Proteins
  • Chloride Channels
  • Helminth Proteins
  • MOD-1 protein, C elegans
  • Serotonin

Associated data

  • GENBANK/AF303088