Abstract
Gamma-aminobutyric acid (GABA) mediates fast inhibitory neurotransmission by activating anion-selective ligand-gated ion channels. Although electrophysiological studies indicate that GABA may activate cation-selective ligand-gated ion channels in some cell types, such a channel has never been characterized at the molecular level. Here we show that GABA mediates enteric muscle contraction in the nematode Caenorhabditis elegans via the EXP-1 receptor, a cation-selective ligand-gated ion channel. The EXP-1 protein resembles ionotropic GABA receptor subunits in almost all domains. In the pore-forming domain of EXP-1, however, the residues that confer anion selectivity are exchanged for those that specify cation selectivity. When expressed in Xenopus laevis oocytes, EXP-1 forms a GABA receptor that is permeable to cations and not anions. We conclude that some of the excitatory functions assigned to GABA are mediated by cation channels rather than by anion channels.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Analysis of Variance
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Animals
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Antigens, Protozoan / chemistry
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Antigens, Protozoan / genetics
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Antigens, Protozoan / metabolism
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Antigens, Protozoan / physiology*
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Barium Compounds / pharmacology
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Bicuculline / pharmacology
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Caenorhabditis elegans
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Cations / metabolism*
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Chloride Channels
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Chlorides / metabolism
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Chlorides / pharmacology
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Cloning, Molecular / methods
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Dose-Response Relationship, Drug
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Electric Conductivity
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GABA Antagonists / pharmacology
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Ganglionic Blockers / pharmacology
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Gastrointestinal Tract / drug effects
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Gastrointestinal Tract / metabolism
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Green Fluorescent Proteins
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Humans
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Luminescent Proteins / metabolism
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Mecamylamine / pharmacology
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Muscle Contraction
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Muscles / drug effects
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Muscles / metabolism
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Mutagenesis, Site-Directed
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Neuromuscular Junction / metabolism
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Oocytes / drug effects
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Patch-Clamp Techniques / methods
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Phylogeny
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Picrotoxin / pharmacology
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RNA, Messenger / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Sequence Alignment
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Sodium / metabolism
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Transfection
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Xenopus laevis
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gamma-Aminobutyric Acid / pharmacology
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gamma-Aminobutyric Acid / physiology*
Substances
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Antigens, Protozoan
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Barium Compounds
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Cations
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Chloride Channels
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Chlorides
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GABA Antagonists
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Ganglionic Blockers
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Luminescent Proteins
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QF116 antigen, Plasmodium falciparum
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RNA, Messenger
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barium chloride
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Picrotoxin
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Green Fluorescent Proteins
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gamma-Aminobutyric Acid
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Mecamylamine
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Sodium
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Bicuculline