Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+

doi:10.1016/0896-6273(90)90337-F

Neuron

Volume 5, Issue 6, December 1990, Pages 781-788

https://doi.org/10.1016/0896-6273(90)90337-F Get rights and content

Abstract

γ-Aminobutyric acid receptor (GABA_AR) channels in different neurons display heterogeneous functional properties. Molecular cloning revealed a large number of GABA_AR subunits that assemble into GABA_AR subtypes with different functional properties, suggesting that the subunit combination determines the functional properties of the receptor. In this study, the subunit composition of GABA_ARs is related to a functional distinction between Zn²⁺-sensitive and Zn²⁺-insensitive receptor subtypes. GABA_ARs reconstituted in transiently transfected fibroblasts from combinations of cDNAs encoding α and β subunits are potently blocked by Zn²⁺. The presence of a γ subunit in any combination with the other subunits leads to the formation of GABA_ARs that are almost insensitive to Zn²⁺. These data provide a structural correlate to the functional heterogeneity of the action of Zn²⁺ on GABA_ARs in native membranes and show that Zn²⁺ insensitivity of GABA-activated currents indicates the presence of a γ-subunit in the assembled GABA_AR channel.

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Neuron

Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+

Abstract

Neuron

Brain Res.

FEBS Lett.

Brain Res.

Brain Res.

Neuron

Neurosci. Lett.

Neuron

FEBS Lett.

Multiple mechanisms of antagonism of γ-aminobutyric acid (GABA) responses

Cell Mol. Neurobiol.

Selective release of endogenous zinc from the hippocampal mossy fibers in situ

Brain Res.

Release of endogenous Zn2+ from brain tissue during activity

Nature

Single subunits of the GABAA receptor form ion channels with properties of the native receptor

Science

High-efficiency transformation of mammalian cells by plasmid DNA

Mol. Cell. Biol.

Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches

Pfügers Arch.

Electron microscopical localization of the zinc in hippocampal mossy fibre synapses by a modified sulfide silver procedure

Histochemie

Stimulation-induced uptake and release of zinc in hippocampal slices

Nature

Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes

Nature

Blocking effects of cobalt and related ions on the γ-aminobutyric acid-induced current in turtle retinal cones

J. Physiol.

Structural and functional basis for GABAA receptor heterogeneity

Nature

Functional and molecular distinction between recombinant rat GABA_A receptor subtypes by Zn²⁺

Release of endogenous Zn²⁺ from brain tissue during activity

Single subunits of the GABA_A receptor form ion channels with properties of the native receptor

Structural and functional basis for GABA_A receptor heterogeneity