Dominant GABAA receptor/Cl channel kinetics correlate with the relative expressions of α2, α3, α5 and β3 subunits in embryonic rat neurones

Authors

  • Serafini,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Maric,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Maric,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Ma,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Fritschy,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Zhang,

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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  • Barker

    1. 1 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, 21Institute of Pharmacology, University of Zurich, Switzerland, 32Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
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Abstract

The embryonic appearance of GABAergic cells and signals in the rat nervous system coincides with the appearance of transcripts encoding some but not all of the subunits forming GABAA receptor/Cl channels. Quantitative in situ hybridization studies reveal higher variabilities in α2 and α3 subunit transcripts relative to others examined (α5, β2, β3 and γ2) in six spinal and supraspinal regions. Immunocytochemistry of cells dissociated from the embryonic CNS shows that α2 and α3 subunits are detectable in differentiating neurones. FACS analyses of dissociated cells immunostained with α2- or α3- antibodies reveal immunopositive subpopulations of variable size in each region. Whole-cell recordings of acutely adherent neurones show that GABA activates Cl currents whose fluctuations characteristically vary depending on a neurone’s region of origin. Spectral analyses indicate a predominance of the low frequency (< 5 Hz) components, which vary regionally. Regression analyses reveal that (i) channel properties correlate with subunit transcript levels and (ii) dominant channel kinetics correlate with α2 and α3 subunit transcripts indexed as a ratio and with coexpressions of α5 and β3. The correlations strongly suggest that α3 subunits in embryonic neurones are expressed in native receptor/channel complexes with slower kinetics than those containing α2 without α3 subunits. Thus, GABAA receptor/Cl channels in these embryonic neurones may be encoded by the six transcripts (α2, α3, α5, and β2, β3, and γ2) with proportions of α2, α3, α5, and β3 subunits critical in determining their dominant kinetics.

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