Genetic manipulations of GABAA receptor in mice make inhibition exciting

被引:39
作者
Vicini, S
Ortinski, P
机构
[1] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA
[2] Georgetown Univ, Sch Med, Interdisciplinary Program Neurosci, Washington, DC USA
关键词
GABA(A) receptors; inhibitory synapses; benzodiazepine; neurosteroids; knock-in; knock-out; transgenic mice; GABA;
D O I
10.1016/j.pharmthera.2004.06.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The inhibitory nernotransmitter gamma-aminobutyric acid (GABA) plays an important role in brain development and behavior. GABA(A) receptor subunits knock-out and knock-in mice have proven that GABA(A) receptors are involved in control of motor coordination, learning, and memory and play a role in anxiety, panic, and epileptogenesis. In addition, these receptors are involved in the molecular mechanisms of action of many drugs and participate actively in cortical plasticity. The use of genetically engineered mice has perhaps never been as successful as in understanding the importance of the heterogeneity of GABA(A) receptors. We review these findings and speculate on the new directions that the use of mice with altered expression of GABA(A) receptor subunits may provide. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:109 / 120
页数:12
相关论文
共 127 条
[1]   α4β3δ GABAA receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential [J].
Adkins, CE ;
Pillai, GV ;
Kerby, J ;
Bonnert, TP ;
Haldon, C ;
McKernan, RM ;
Gonzalez, JE ;
Oades, K ;
Whiting, PJ ;
Simpson, PB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38934-38939
[2]   Postsynaptic clustering of γ-aminobutyric acid type A receptors by the γ3 subunit in vivo [J].
Baer, K ;
Essrich, C ;
Benson, JA ;
Benke, D ;
Bluethmann, H ;
Fritschy, JM ;
Lüscher, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12860-12865
[3]   Rescue of γ2 subunit-deficient mice by transgenic overexpression of the GABAA receptor γ2S or γ2L subunit isoforms [J].
Baer, K ;
Essrich, C ;
Balsiger, S ;
Wick, MJ ;
Harris, RA ;
Fritschy, JM ;
Lüscher, B .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (07) :2639-2643
[4]   Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells [J].
Banks, MI ;
Pearce, RA .
JOURNAL OF NEUROSCIENCE, 2000, 20 (03) :937-948
[5]  
Barnard EA, 1998, PHARMACOL REV, V50, P291
[6]  
BENKE D, 1994, J BIOL CHEM, V269, P27100
[7]   Molecular mechanisms of tolerance to and withdrawal of GABAA receptor modulators [J].
Biggio, G ;
Dazzi, L ;
Biggio, F ;
Mancuso, L ;
Talani, G ;
Busonero, F ;
Mostallino, MC ;
Sanna, E ;
Follesa, P .
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2003, 13 (06) :411-423
[8]   GABAA receptor α1 and β2 subunit null mutant mice:: Behavioral responses to ethanol [J].
Blednov, YA ;
Walker, D ;
Alva, H ;
Creech, K ;
Findlay, G ;
Harris, RA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 305 (03) :854-863
[9]   Deletion of the α1 or β2 subunit of GABAA receptors reduces actions of alcohol and other drugs [J].
Blednov, YA ;
Jung, S ;
Alva, H ;
Wallace, D ;
Rosahl, T ;
Whiting, PJ ;
Harris, RA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (01) :30-36
[10]   GABAA receptor composition is determined by distinct assembly signals within α and β subunits [J].
Bollan, K ;
King, D ;
Robertson, LA ;
Brown, K ;
Taylor, PM ;
Moss, SJ ;
Connolly, CN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (07) :4747-4755