Pentobarbital differentially modulates alpha1beta3delta and alpha1beta3gamma2L GABAA receptor currents

Molecular Pharmacology
Hua-Jun FengR L Macdonald

Abstract

GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphabetadelta GABAA receptors, thought to mediate tonic (extra- or perisynaptic) inhibition, are unknown. Using ultrafast drug delivery and single channel recording techniques, we demonstrate isoform-specific pentobarbital modulation of low-efficacy, minimally desensitizing alpha1beta3 currents and high-efficacy, rapidly desensitizing alpha1beta3gamma2L currents. Specifically, with saturating concentrations of GABA, pentobarbital substantially potentiated peak alpha1beta3delta receptor currents but failed to potentiate peak alpha1beta3gamma2L receptor currents. Also, pentobarbital had opposite effects on the desensitization of alpha1beta3delta (increased) and alpha1beta3gamma2L (decreased) receptor currents evoked by saturating GABA. Pentobarbital increased steady-state alpha1beta3delta receptor single channel open duration primarily by introducing a longer duration open state, whereas for alpha1beta3gamma2L receptor ch...Continue Reading

References

Jun 2, 1980·Brain Research·R A Nicoll, J M Wojtowicz
Sep 1, 1995·Trends in Pharmacological Sciences·J J LambertJ A Peters
Feb 1, 1996·British Journal of Pharmacology·S A ThompsonK A Wafford
Dec 1, 1996·The Journal of Physiology·J M RhoM A Rogawski
Feb 17, 1998·The European Journal of Neuroscience·J R WooltortonT G Smart
Apr 21, 1999·Brain Research. Developmental Brain Research·C Rovira, Y Ben-Ari
Aug 11, 1999·Trends in Neurosciences·R Rupprecht, F Holsboer
May 12, 2000·British Journal of Pharmacology·G Akk, J H Steinbach
Dec 18, 2001·The Journal of Physiology·J H Steinbach, G Akk
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brandon M StellIstvan Mody
Nov 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·M WallnerR W Olsen
Feb 18, 2004·The Journal of Physiology·Gustav AkkJoe Henry Steinbach

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Citations

Dec 28, 2011·Documenta Ophthalmologica. Advances in Ophthalmology·Charlene B Y KimT Michael Nork
Dec 8, 2005·Visual Neuroscience·E T BrownR Barlow
Aug 14, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Keith B HengenStephen M Johnson
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Delia BelelliDavid W Cope
Mar 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Howard P GoodkinJaideep Kapur
Feb 10, 2007·Neuropharmacology·David A MathersErnest Puil
May 21, 2013·Seizure : the Journal of the British Epilepsy Association·L John Greenfield
Jun 5, 2012·Journal of Molecular Biology·Timothy S CarpenterFelice C Lightstone
Jul 4, 2006·Pharmacology & Therapeutics·Martin WallnerRichard W Olsen
Jul 19, 2014·Journal of Psychiatric Practice·Lucio GhioMario Amore
Dec 14, 2018·The Journal of Biological Chemistry·Carla Gottschald ChiodiTim G Hales
Dec 12, 2012·Epilepsia·Wolfgang Löscher, Michael A Rogawski
Nov 6, 2018·The Journal of Pharmacology and Experimental Therapeutics·Yiwei LiaoHua-Jun Feng
May 27, 2006·The Journal of Pharmacology and Experimental Therapeutics·Brandon C Drafts, Janet L Fisher
Nov 8, 2005·Molecular Pharmacology·S KhomS Hering
Aug 28, 2004·Molecular Pharmacology·Hua-Jun Feng, Robert L Macdonald
Jun 24, 2017·Neurotoxicity Research·Stefanie EndesfelderChristoph Bührer
Jan 3, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hua-Jun Feng, Stuart A Forman
Nov 26, 2010·Neuropharmacology·Leonardo DionisioMaría Del Carmen Esandi

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