A new naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol (original) (raw)

References

  1. Sieghart, W. & Sperk, G. Subunit composition, distribution and function of GABAA receptor subtypes. Curr. Top. Med. Chem. 2, 795–816 (2002).
    Article CAS Google Scholar
  2. McKernan, R.M. & Whiting, P.J. Which GABAA receptor subtypes really occur in the brain? Trends Neurosci. 19, 139–143 (1996).
    Article CAS Google Scholar
  3. Whiting, P.J. GABAA receptor subtypes in the brain: a paradigm for CNS drug discovery? Drug Discov. Today 8, 445–450 (2003).
    Article CAS Google Scholar
  4. Sur, C. et al. Preferential co-assembly of α4 and δ subunits of the γ-aminobutyric acid A receptor in rat thalamus. Mol. Pharmacol. 56, 110–115 (1999).
    Article CAS Google Scholar
  5. Jones, A. et al. Ligand-gated ion channel subunit partnerships: GABAA receptor α6 subunit gene inactivation inhibits δ subunit expression. J. Neurosci. 17, 1350–1362 (1997).
    Article CAS Google Scholar
  6. Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W. & Sperk, G. GABAA receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101, 815–850 (2000).
    Article CAS Google Scholar
  7. Sun, C., Sieghart, W. & Kapur, J. Distribution of alpha1, alpha4, gamma2, and delta subunits of GABAA receptors in hippocampal granule cells. Brain Res. 1029, 207–216 (2004).
    Article CAS Google Scholar
  8. Peng, Z. et al. GABAA receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrain. J. Comp. Neurol. 446, 179–197 (2002).
    Article CAS Google Scholar
  9. Peng, Z., Huang, C.S., Stell, B.M., Mody, I. & Houser, C.R. Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy. J. Neurosci. 24, 8629–8639 (2004).
    Article CAS Google Scholar
  10. Sperk, G., Schwarzer, C., Tsunashima, K., Fuchs, K. & Sieghart, W. GABAA receptor subunits in the rat hippocampus I: immunocytochemical distribution of 13 subunits. Neuroscience 80, 987–1000 (1997).
    Article CAS Google Scholar
  11. Gao, B. & Fritschy, J.M. Selective allocation of GABAA receptors containing the alpha 1 subunit to neurochemically distinct subpopulations of rat hippocampal interneurons. Eur. J. Neurosci. 6, 837–853 (1994).
    Article CAS Google Scholar
  12. Brunig, I., Scotti, E., Sidler, C. & Fritschy, J.M. Intact sorting, targeting, and clustering of gamma-aminobutyric acid A receptor subtypes in hippocampal neurons in vitro. J. Comp. Neurol. 443, 43–55 (2002).
    Article CAS Google Scholar
  13. Esclapez, M., Chang, D.K. & Houser, C.R. Subpopulations of GABA neurons in the dentate gyrus express high levels of the alpha 1 subunit of the GABAA receptor. Hippocampus 6, 225–238 (1996).
    Article CAS Google Scholar
  14. Somogyi, P., Fritschy, J.M., Benke, D., Roberts, J.D. & Sieghart, W. The gamma2 subunit of the GABAA receptor is concentrated in synaptic junctions containing the alpha 1 and beta 2/3 subunits in hippocampus, cerebellum and globus pallidus. Neuropharmacology 35, 1425–1444 (1996).
    Article CAS Google Scholar
  15. Essrich, C., Lorez, M., Benson, J.A., Fritschy, J.M. & Luscher, B. Postsynaptic clustering of major GABAA receptor subtypes requires the gamma2 subunit and gephyrin. Nat. Neurosci. 1, 563–571 (1998).
    Article CAS Google Scholar
  16. Araujo, F., Ruano, D. & Vitorica, J. Absence of association between delta and gamma2 subunits in native GABAA receptors from rat brain. Eur. J. Pharmacol. 347, 347–353 (1998).
    Article CAS Google Scholar
  17. Quirk, K., Whiting, P.J., Ragan, C.I. & McKernan, R.M. Characterization of delta-subunit containing GABAA receptors from rat brain. Eur. J. Pharmacol. 290, 175–181 (1995).
    Article CAS Google Scholar
  18. Nusser, Z., Sieghart, W. & Somogyi, P. Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J. Neurosci. 18, 1693–1703 (1998).
    Article CAS Google Scholar
  19. Wei, W., Zhang, N., Peng, Z., Houser, C.R. & Mody, I. Perisynaptic localization of delta subunit-containing GABAA receptors and their activation by GABA spillover in the mouse dentate gyrus. J. Neurosci. 23, 10650–10661 (2003).
    Article CAS Google Scholar
  20. Mody, I. & Pearce, R.A. Diversity of inhibitory neurotransmission through GABAA receptors. Trends Neurosci. 27, 569–575 (2004).
    Article CAS Google Scholar
  21. Farrant, M. & Nusser, Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nat. Rev. Neurosci. 6, 215–229 (2005).
    Article CAS Google Scholar
  22. Scimemi, A., Semyanov, A., Sperk, G., Kullmann, D.M. & Walker, M.C. Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J. Neurosci. 25, 10016–10024 (2005).
    Article CAS Google Scholar
  23. Wei, W., Faria, L.C. & Mody, I. Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABAA receptors in hippocampal neurons. J. Neurosci. 24, 8379–8382 (2004).
    Article CAS Google Scholar
  24. Maguire, J.L., Stell, B.M., Rafizadeh, M. & Mody, I. Ovarian cycle–linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat. Neurosci. 8, 797–804 (2005).
    Article CAS Google Scholar
  25. Nusser, Z. & Mody, I. Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells. J. Neurophysiol. 87, 2624–2628 (2002).
    Article CAS Google Scholar
  26. Stell, B.M., Brickley, S.G., Tang, C.Y., Farrant, M. & Mody, I. Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc. Natl. Acad. Sci. USA 100, 14439–14444 (2003).
    Article CAS Google Scholar
  27. Jia, F. et al. An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons. J. Neurophysiol. 94, 4491–4501 (2005).
    Article CAS Google Scholar
  28. Cope, D.W., Hughes, S.W. & Crunelli, V. GABAA receptor-mediated tonic inhibition in thalamic neurons. J. Neurosci. 25, 11553–11563 (2005).
    Article CAS Google Scholar
  29. Hanchar, H.J., Dodson, P.D., Olsen, R.W., Otis, T.S. & Wallner, M. Alcohol-induced motor impairment caused by increased extrasynaptic GABAA receptor activity. Nat. Neurosci. 8, 339–345 (2005).
    Article CAS Google Scholar
  30. Wallner, M., Hanchar, H.J. & Olsen, R.W. Ethanol enhances alpha4 beta3 delta and alpha6 beta3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc. Natl. Acad. Sci. USA 100, 15218–15223 (2003).
    Article CAS Google Scholar
  31. Sundstrom-Poromaa, I. et al. Hormonally regulated α4β2δ GABAA receptors are a target for alcohol. Nat. Neurosci. 5, 721–722 (2002).
    Article CAS Google Scholar
  32. Wohlfarth, K.M., Bianchi, M.T. & MacDonald, R.L. Enhanced neurosteroid potentiation of ternary GABAA receptors containing the delta subunit. J. Neurosci. 22, 1541–1549 (2002).
    Article CAS Google Scholar
  33. Bianchi, M.T., Haas, K.F. & MacDonald, R.L. Alpha1 and alpha6 subunits specify distinct desensitization, deactivation and neurosteroid modulation of GABAA receptors containing the delta subunit. Neuropharmacology 43, 492–502 (2002).
    Article CAS Google Scholar
  34. Goldstein, P.A. et al. Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABAA receptor alpha1 subunit. J. Neurophysiol. 88, 3208–3217 (2002).
    Article CAS Google Scholar
  35. Glykys, J. & Mody, I. Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABAA receptor alpha5 subunit-deficient mice. J. Neurophysiol. 95, 2796–2807 (2006).
    Article CAS Google Scholar
  36. Borghese, C.M. et al. The delta subunit of gamma-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol. J. Pharmacol. Exp. Ther. 316, 1360–1368 (2006).
    Article CAS Google Scholar
  37. Chandra, D. et al. GABAA receptor alpha4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proc. Natl. Acad. Sci. USA 103, 15230–15235 (2006).
    Article CAS Google Scholar
  38. Korpi, E.R. et al. Altered receptor subtypes in the forebrain of GABAA receptor delta subunit-deficient mice: recruitment of gamma2 subunits. Neuroscience 109, 733–743 (2002).
    Article CAS Google Scholar
  39. Hamann, M., Rossi, D.J. & Attwell, D. Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33, 625–633 (2002).
    Article CAS Google Scholar
  40. Wall, M.J. Furosemide reveals heterogeneous GABAA receptor expression at adult rat Golgi cell to granule cell synapses. Neuropharmacology 43, 737–749 (2002).
    Article CAS Google Scholar
  41. Wafford, K.A. et al. Differentiating the role of gamma-aminobutyric acid type A (GABAA) receptor subtypes. Biochem. Soc. Trans. 32, 553–556 (2004).
    Article CAS Google Scholar
  42. Poltl, A., Hauer, B., Fuchs, K., Tretter, V. & Sieghart, W. Subunit composition and quantitative importance of GABAA receptor subtypes in the cerebellum of mouse and rat. J. Neurochem. 87, 1444–1455 (2003).
    Article Google Scholar
  43. Hanchar, H.J., Wallner, M. & Olsen, R.W. Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer? Life Sci. 76, 1–8 (2004).
    Article CAS Google Scholar
  44. Mihalek, R.M. et al. GABAA receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. Alcohol. Clin. Exp. Res. 25, 1708–1718 (2001).
    CAS PubMed Google Scholar
  45. Kralic, J.E. et al. Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of gamma-aminobutyric acid type A receptor alpha1 subunit knockout mice. J. Comp. Neurol. 495, 408–421 (2006).
    Article CAS Google Scholar
  46. Ogris, W. et al. Investigation of the abundance and subunit composition of GABAA receptor subtypes in the cerebellum of alpha1-subunit-deficient mice. J. Neurochem. 96, 136–147 (2006).
    Article CAS Google Scholar
  47. Ponomarev, I. et al. Transcriptional signatures of cellular plasticity in mice lacking the alpha1 subunit of GABAA receptors. J. Neurosci. 26, 5673–5683 (2006).
    Article CAS Google Scholar
  48. Sur, C. et al. Loss of the major GABAA receptor subtype in the brain is not lethal in mice. J. Neurosci. 21, 3409–3418 (2001).
    Article CAS Google Scholar
  49. Weiner, J.L., Valenzuela, C.F., Watson, P.L., Frazier, C.J. & Dunwiddie, T.V. Elevation of basal protein kinase C activity increases ethanol sensitivity of GABAA receptors in rat hippocampal CA1 pyramidal neurons. J. Neurochem. 68, 1949–1959 (1997).
    Article CAS Google Scholar
  50. Weiner, J.L., Gu, C. & Dunwiddie, T.V. Differential ethanol sensitivity of subpopulations of GABAA synapses onto rat hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77, 1306–1312 (1997).
    Article CAS Google Scholar
  51. Han, Z.S., Buhl, E.H., Lorinczi, Z. & Somogyi, P. A high degree of spatial selectivity in the axonal and dendritic domains of physiologically identified local-circuit neurons in the dentate gyrus of the rat hippocampus. Eur. J. Neurosci. 5, 395–410 (1993).
    Article CAS Google Scholar
  52. Mihalek, R.M. et al. Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc. Natl. Acad. Sci. USA 96, 12905–12910 (1999).
    Article CAS Google Scholar

Download references