Drosophila melanogaster GRD and LCCH3 subunits form heteromultimeric GABA-gated cation channels.
In addition to its action as a fast inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is thought to mediate excitatory action by activating cation currents in some cell types in invertebrates. However, to date no GABA receptor capable of mediating such action has been identified at the molecular level in insects. Using a systematic expression screening approach, we found that the Drosophila ligand-gated ion channel subunits GRD and LCCH3 combine to form cation-selective GABA-gated ion channels when coexpressed in Xenopus laevis oocytes. The heteromultimeric receptor is activated by GABA (EC50=4.5 microm), muscimol (EC50=4.8 microm) and trans-4-aminocrotonic acid (EC50=104.5 microm), and partially by cis-4-aminocrotonic acid (EC50=106.3 microm). Picrotoxin effectively blocked the GABA-gated channel (IC50=0.25 microm), but bicuculline, TPMTA, dieldrin and lindane did not. The benzodiazepines flunitrazepam and diazepam did not potentiate the GABA-evoked current. Our data suggest that heteromultimeric channels composed of GRD and LCCH3 subunits form GABA-gated cation channels in insects.
Gisselmann
Günter
G
Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum, Germany. guenter.gisselmann@ruhr-uni-bochum.de
Plonka
Justina
J
Pusch
Hermann
H
Hatt
Hanns
H
D000818:Animals; D002412:Cations; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D004331:Drosophila melanogaster; D018682:GABA Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016415:Sequence Alignment; D014982:Xenopus laevis
D002412:Cations; D018118:Chloride Channels; D018682:GABA Agents; D007473:Ion Channels; D021122:Protein Subunits; D018079:Receptors, GABA