Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.
- M. Majewska, N. Harrison, R. D. Schwartz, J. Barker, S. Paul
- Biology, ChemistryScience
- 23 May 1986
Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability.
Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors
- S. Mihic, Q. Ye, N. Harrison
- BiologyNature
- 25 September 1997
Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.
Extrasynaptic GABAA Receptors: Form, Pharmacology, and Function
- D. Belelli, N. Harrison, J. Maguire, R. Macdonald, M. Walker, D. Cope
- BiologyJournal of Neuroscience
- 14 October 2009
This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents and identifies them as a major player in both physiological and pathophysiological processes.
Coupling of agonist binding to channel gating in the GABAA receptor
- T. Kash, A. Jenkins, Jill C. Kelley, J. Trudell, N. Harrison
- Biology, ChemistryNature
- 16 January 2003
It is shown that optimal gating in the GABAA receptor, a member of the LGIC superfamily, is dependent on electrostatic interactions between the negatively charged Asp 57 and Asp 149 residues in extracellular loops 2 and 7, and the positively charged Lys 279 residue in the transmembrane 2–3 linker region of the α1-subunit.
An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons.
- F. Jia, L. Pignataro, C. M. Schofield, M. Yue, N. Harrison, P. A. Goldstein
- BiologyJournal of Neurophysiology
- 1 December 2005
It is concluded that thalamic VB neurons express extrasynaptic GABA(A) receptors that are highly sensitive to GABA and THIP and that these receptors are most likely made up of alpha(4)beta(2)delta subunits.
General anaesthetic actions on ligand-gated ion channels
- M. Krasowski, N. Harrison
- BiologyCellular and Molecular Life Sciences (CMLS)
- 15 August 1999
The last 10 years have witnessed an explosion of studies of anaesthetic modulation of recombinant ligand-gated ion channels, including recent studies which utilize chimeric and mutated receptors to identify regions of ligands-gating ion channels important for the actions of general anaesthetics.
GABAA receptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol
- D. Chandra, F. Jia, G. Homanics
- BiologyProceedings of the National Academy of Sciences
- 10 October 2006
It is demonstrated that tonic inhibition in dentate granule cells and thalamic relay neurons is mediated by extrasynaptic GABAA-Rs containing the α4 subunit and that gaboxadol achieves its effects via the activation of this GabAA-R subtype.
Emerging molecular mechanisms of general anesthetic action.
- H. Hemmings, M. Akabas, P. A. Goldstein, J. Trudell, B. Orser, N. Harrison
- Biology, ChemistryTIPS - Trends in Pharmacological Sciences
- 1 October 2005
Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior.
- G. Homanics, T. Delorey, R. Olsen
- Biology, PsychologyProceedings of the National Academy of Sciences…
- 1997
Hyperactivity, lack of coordination, and seizures in beta3-deficient mice are consistent with reduced presynaptic inhibition in spinal cord and impaired inhibition in higher cortical centers and/or pleiotropic developmental defects.
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
- M. Wick, S. Mihic, R. Harris
- Biology, MedicineProceedings of the National Academy of Sciences…
- 26 May 1998
The results support the existence of alcohol binding pockets in these membrane proteins and suggest that the amino acid residues present at these positions can control the size of the alcohol binding cavity.
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