The Receptors. Volume 27

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1 The Receptors Volume 27 Series Editor Giuseppe di Giovanni Department of Physiology & Biochemistry Faculty of Medicine and Surgery, University of Malta, Malta, Italy

2 The Receptors book Series, founded in the 1980 s, is a broad-based and wellrespected series on all aspects of receptor neurophysiology. The series presents published volumes that comprehensively review neural receptors for a specific hormone or neurotransmitter by invited leading specialists. Particular attention is paid to in-depth studies of receptors role in health and neuropathological processes. Recent volumes in the series cover chemical, physical, modeling, biological, pharmacological, anatomical aspects and drug discovery regarding different receptors. All books in this series have, with a rigorous editing, a strong reference value and provide essential up-to-date resources for neuroscience researchers, lecturers, students and pharmaceutical research. More information about this series at

3 Adam C. Errington Giuseppe Di Giovanni Vincenzo Crunelli Editors Extrasynaptic GABA A Receptors 1 3

4 Editors Adam C. Errington Neuroscience and Mental Health Research Institute Institute of Psychological Medicine and Clinical Neuroscience School of Medicine Cardiff University Cardiff United Kingdom Vincenzo Crunelli School of Biosciences Cardiff University Cardiff United Kingdom Giuseppe Di Giovanni Dept. of Physiology & Biochemistry University of Malta Msida MSD Malta ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media, LLC 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (

5 Contents 1 Extrasynaptic GABA A Receptors... 1 Adam C. Errington 2 Extrasynaptic GABA A Receptors: Subunit Composition, Distribution, and Regulation Jean-Marc Fritschy and Patrizia Panzanelli 3 Biophysical Properties of Recombinant γ2- and δ-subunit Containing GABA A Receptors Robert L. Macdonald and Emmanuel J. Botzolakis 4 The Pharmacology of Extrasynaptic GABA A Receptors Keith A Wafford 5 Neurosteroids and Extrasynaptic GABA A Receptors William M. Connelly 6 Sources of GABA That Activate Extrasynaptic GABA A Receptors Damian Bright, Catriona Houston and Stephen Brickley 7 GPCR Modulation of Extrasynapitic GABA A Receptors William M. Connelly, Adam C. Errington, Josue G. Yagüe, Anna Cavaccini, Vincenzo Crunelli and Giuseppe Di Giovanni 8 Extrasynaptic GABA A Receptors and Tonic Inhibition in Spinal Cord Emanuel Loeza-Alcocer, Carmen Andrés, Justo Aguilar, Ricardo Felix and Rodolfo Delgado-Lezama 9 The Role of Peri-synaptic GABA Receptors After Stroke Andrew N. Clarkson and Mary Chebib v

6 vi Contents 10 The Role of Extrasynaptic GABA A Receptors in Focal Epilepsy Matthew C. Walker and Ivan Pavlov 11 Gain-of-Function of Thalamic Extrasynaptic GABA-A Receptors in Typical Absence Seizures Vincenzo Crunelli, Giuseppe Di Giovanni, H. Rheinallt Parri and Adam C. Errington 12 GABAergic Control of the Hypothalamic Pituitary Adrenal (HPA) Axis: Role of Extrasynaptic GABA A Receptors Jamie Maguire 13 Tonic GABA A -Receptor-Mediated Inhibition in Fragile-X Syndrome: A Cause of Dysfunction or a Pathway for a Cure? Brandon S. Martin and Molly M. Huntsman Index

7 Contributors Justo Aguilar Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav- IPN), Mexico City, Mexico Carmen Andrés Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav- IPN), Mexico City, Mexico Emmanuel J. Botzolakis Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA Stephen Brickley Biophysics Section, Department of Life Sciences, Imperial College London, London, UK Damian Bright Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK Anna Cavaccini Neuroscience Division, Cardiff School of Biosciences Cardiff University, Cardiff, UK Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy Mary Chebib Department of Pharmacy A15, University of Sydney, Sydney, NSW, Australia Andrew N. Clarkson Departments of Anatomy and Psychology, University of Otago, Dunedin, New Zealand William M. Connelly Neuroscience Division, Cardiff School of Biosciences, Cardiff University, Cardiff, UK Vincenzo Crunelli Neuroscience Division, Cardiff School of Biosciences, Cardiff University, Cardiff, UK vii

8 viii Contributors Rodolfo Delgado-Lezama Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico Giuseppe Di Giovanni Department of Physiology and Biochemistry, Faculty of Medicine, Malta University, Msida, Malta Adam C. Errington Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK Ricardo Felix Department of Cell Biology, Cinvestav-IPN, Mexico City, Mexico Jean-Marc Fritschy Institute of Pharmacology and Toxicology, University of Zurich, Zürich, Zürich, Switzerland Catriona Houston Biophysics Section, Department of Life Sciences, Imperial College London, London, UK Molly M. Huntsman Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, USA Emanuel Loeza-Alcocer Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico Robert L. Macdonald Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA Jamie Maguire Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA Brandon S. Martin Children s National Medical Center, Washington, DC, USA Patrizia Panzanelli Department of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy H. Rheinallt Parri School of Life and Health Sciences, Aston University, Birmingham, UK Ivan Pavlov Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK Keith A Wafford Eli Lilly UK, Windlesham, Surrey, UK

9 Contributors ix Matthew C. Walker Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK Josue G. Yagüe Neuroscience Division, Cardiff School of Biosciences Cardiff University, Cardiff, UK Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK

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