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EXP-1 is an excitatory GABA-gated cation channel

Nature Neuroscience volume 6, pages 1145–1152 (2003)Cite this article

Abstract

γ-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.

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Figure 1: Phenotypic characterization and molecular cloning of exp-1.
Figure 2: Sequence alignment of EXP-1 and GABA receptor subunits.
Figure 3: Expression pattern of the exp-1 gene.
Figure 4: EXP-1 is a unique member of the ionotropic GABA receptor family.
Figure 6: EXP-1 contains the molecular determinants for cation selectivity.
Figure 5: EXP-1 is a GABA-gated, cation-selective channel.

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Acknowledgements

We thank K. Schuske for cosmid injections and helpful advice, and M.W. Davis for full-length cDNA predictions, technical assistance and critical readings of this manuscript. The alleles n2570, n2641 and n2676 were isolated in the laboratory of B. Horvitz. We thank J. Thomas for the sa6 allele, discussions and encouragement. A. Coulson and the Sanger Center provided cosmid clones. We thank M. Hollmann for the pSGEM expression vector. We thank the Olivera, McIntosh and Yoshikami labs for X. laevis oocyte isolation and Z. Altun for cell identification. This work was supported by a National Institutes of Health Grant (E.M.J.). A.A.B. is supported by an Epilepsy Foundation of America predoctoral fellowship and a University of Utah predoctoral fellowship.

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  1. Neuroscience Program and Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, 84112-0840, Utah, USA

    Asim A Beg & Erik M Jorgensen

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Correspondence to Erik M Jorgensen.

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Beg, A., Jorgensen, E. EXP-1 is an excitatory GABA-gated cation channel. Nat Neurosci 6, 1145–1152 (2003). https://doi.org/10.1038/nn1136

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