• Br J Anaesth · Jun 2013

    Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists.

    • I Lecker, Y Yin, D S Wang, and B A Orser.
    • Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8.
    • Br J Anaesth. 2013 Jun 1; 110 Suppl 1: i73-81.

    BackgroundAnimal studies have shown that memory deficits in the early post-anaesthetic period can be prevented by pre-treatment with an inverse agonist that preferentially inhibits α5 subunit-containing γ-aminobutyric acid type A (α5GABA(A)) receptors. The goal of this in vitro study was to determine whether inverse agonists that inhibit α5GABA(A) receptors reduce anaesthetic potentiation of GABAA receptor activity.MethodsCultures of hippocampal neurones were prepared from Swiss white mice, wild-type mice (genetic background C57BL/6J and Sv129Ev) and α5GABA(A)receptor null mutant (Gabra5-/-) mice. Whole-cell voltage clamp techniques were used to study the effects of the α5GABA(A) receptor-preferring inverse agonists L-655,708 and MRK-016 on anaesthetic potentiation of GABA-evoked currents.ResultsL-655,708 (50 nM) reduced sevoflurane potentiation of GABA-evoked current in wild-type neurones but not Gabra5-/- neurones, and produced a rightward shift in the sevoflurane concentration-response plot [sevoflurane EC50: 1.9 (0.1) mM; sevoflurane+L-655,708 EC(50): 2.4 (0.2) mM, P<0.05]. Similarly, L-655,708 (50 nM) reduced isoflurane potentiation of GABA-evoked current [isoflurane: 4.0 (0.6) pA pF(-1); isoflurane+L-655,708: 3.1 (0.5) pA pF(-1), P<0.01]. MRK-016 also reduced sevoflurane and isoflurane enhancement of GABA-evoked current [sevoflurane: 1.5 (0.1) pA pF(-1); sevoflurane+MRK-016 (10 nM): 1.2 (0.1) pA pF(-1), P<0.05; isoflurane: 3.5 (0.3) pA pF(-1); isoflurane+MRK-016 (1 nM): 2.9 (0.2) pA pF(-1), P<0.05].ConclusionsL-655,708 and MRK-016 reduced the potentiation by inhaled anaesthetics of GABAA receptor activated by a low concentration of GABA. Future studies are required to determine whether this effect contributes to the memory preserving properties of inverse agonists after anaesthesia.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…