EXP-1 is an excitatory GABA-gated cation channel.
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.
Beg
Asim A
AA
Neuroscience Program and Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA.
Jorgensen
Erik M
EM
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017609:Barium Compounds / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D017173:Caenorhabditis elegans; D002412:Cations / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008164:Luminescent Proteins / Q000378:metabolism; D008464:Mecamylamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009469:Neuromuscular Junction / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010802:Phylogeny; D010852:Picrotoxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D000953:Antigens, Protozoan; D017609:Barium Compounds; D001640:Bicuculline; D002412:Cations; D018118:Chloride Channels; D002712:Chlorides; D018756:GABA Antagonists; D005730:Ganglionic Blockers; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008464:Mecamylamine; D010852:Picrotoxin; D012333:RNA, Messenger; D012964:Sodium; D005680:gamma-Aminobutyric Acid; C063362:QF116 antigen, Plasmodium falciparum; C024986:barium chloride