![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
NC Saxena and RL Macdonald
Department of Neurology, University of Michigan Medical School, Ann Arbor, 48104-1687, USA.
Analysis of the composition of cerebellar gamma-aminobutyric acidA (GABAA) receptors (GABARs) with in situ hybridization of GABAR subunit subtype mRNAs [J. Neurosci 12:1063-1076 (1992)] and Western blot analysis and quantitative binding of radioligands to immunopurified receptors from the rat cerebellum [J. Biol. Chem. 269:16020-16028 (1994)] have suggested that GABAR isoforms likely to occur in the cerebellum of adult rats are alpha1betaxgamma2, alpha6betaxgamma2, and alpha6betaxdelta isoforms. Based on these data, GABARs composed of different combinations of rat alpha1, alpha6, beta2, beta3, gamma2L, and delta subunits, corresponding to the three putative cerebellar GABAR isoforms, were transiently expressed in mouse fibroblast cells (L929 cells). Whole-cell currents were recorded from acutely transfected cells to determine whether the alpha1beta2/3gamma2L, alpha6beta2/3gamma2L, and alpha6beta2/3delta GABAR isoforms could form functional receptor channels in L929 cells and to compare their electrophysiological and pharmacological properties. All three putative cerebellar GABAR isoforms showed a high efficiency of expression of functional GABARs. We chose to study the beta3 and gamma2L subtypes as major representatives of the native subunit subtype proteins. The recombinant alpha1beta3gamma2L, alpha6beta3gamma2L, and alpha6beta3delta GABAR isoforms displayed different affinities (EC50 values) for GABA, differential sensitivity to block by the divalent cation zinc and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3- carboxylate, and differences in enhancement by diazepam. Our results provide an initial characterization of the electrophysiological and pharmacological properties of possible in vivo cerebellar GABAR isoforms and demonstrate that subunit compositions of different GABAR isoforms play a crucial role in determining their properties.
This article has been cited by other articles:
|
|
 |
|
  W. Hevers, S. H. Hadley, H. Luddens, and J. Amin Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABAA Receptors Containing {alpha}6 and {delta} Subunits J. Neurosci., May 14, 2008; 28(20): 5383 - 5393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Herden, N. E. Pardo, R. K. Hajela, Y. Yuan, and W. D. Atchison Differential Effects of Methylmercury on {gamma}-Aminobutyric Acid Type A Receptor Currents in Rat Cerebellar Granule and Cerebral Cortical Neurons in Culture J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 517 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Eugene, C. Depienne, S. Baulac, M. Baulac, J. M. Fritschy, E. Le Guern, R. Miles, and J. C. Poncer GABAA Receptor {gamma}2 Subunit Mutations Linked to Human Epileptic Syndromes Differentially Affect Phasic and Tonic Inhibition J. Neurosci., December 19, 2007; 27(51): 14108 - 14116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Bianchi, E. J. Botzolakis, K. F. Haas, J. L. Fisher, and R. L. Macdonald Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABAA receptor desensitization and deactivation J. Physiol., November 1, 2007; 584(3): 769 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Hadley and J. Amin Rat {alpha}6beta2{delta} GABAA receptors exhibit two distinct and separable agonist affinities J. Physiol., June 15, 2007; 581(3): 1001 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Bright, M. I. Aller, and S. G. Brickley Synaptic Release Generates a Tonic GABAA Receptor-Mediated Conductance That Modulates Burst Precision in Thalamic Relay Neurons J. Neurosci., March 7, 2007; 27(10): 2560 - 2569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bouairi, H. Kamendi, X. Wang, C. Gorini, and D. Mendelowitz Multiple Types of GABAA Receptors Mediate Inhibition in Brain Stem Parasympathetic Cardiac Neurons In the Nucleus Ambiguus J Neurophysiol, December 1, 2006; 96(6): 3266 - 3272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Popik, E. Kostakis, M. Krawczyk, G. Nowak, B. Szewczyk, P. Krieter, Z. Chen, S. J. Russek, T. T. Gibbs, D. H. Farb, et al. The Anxioselective Agent 7-(2-Chloropyridin-4-yl)pyrazolo-[1,5-a]-pyrimidin-3-yl](pyridin-2-yl)methanone (DOV 51892) Is More Efficacious Than Diazepam at Enhancing GABA-Gated Currents at {alpha}1 Subunit-Containing GABAA Receptors J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1244 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. C. Cuzon, P. W. Yeh, Q. Cheng, and H. H. Yeh Ambient GABA Promotes Cortical Entry of Tangentially Migrating Cells Derived from the Medial Ganglionic Eminence Cereb Cortex, October 1, 2006; 16(10): 1377 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. I. Ortinski, J. R. Turner, A. Barberis, G. Motamedi, R. P. Yasuda, B. B. Wolfe, K. J. Kellar, and S. Vicini Deletion of the GABAA Receptor {alpha}1 Subunit Increases Tonic GABAA Receptor Current: A Role for GABA Uptake Transporters J. Neurosci., September 6, 2006; 26(36): 9323 - 9331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Drasbek and K. Jensen THIP, a Hypnotic and Antinociceptive Drug, Enhances an Extrasynaptic GABAA Receptor-mediated Conductance in Mouse Neocortex Cereb Cortex, August 1, 2006; 16(8): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Hanchar, P. Chutsrinopkun, P. Meera, P. Supavilai, W. Sieghart, M. Wallner, and R. W. Olsen From the Cover: Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to {alpha}4/6beta3{delta} GABAA receptors PNAS, May 30, 2006; 103(22): 8546 - 8551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wallner, H. J. Hanchar, and R. W. Olsen From the Cover: Low-dose alcohol actions on {alpha}4beta3{delta} GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513 PNAS, May 30, 2006; 103(22): 8540 - 8545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Santhakumar, H. J. Hanchar, M. Wallner, R. W. Olsen, and T. S. Otis Contributions of the GABAA receptor alpha6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the alpha6 gene. J. Neurosci., March 22, 2006; 26(12): 3357 - 3364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mtchedlishvili and J. Kapur High-Affinity, Slowly Desensitizing GABAA Receptors Mediate Tonic Inhibition in Hippocampal Dentate Granule Cells Mol. Pharmacol., February 1, 2006; 69(2): 564 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Jia, L. Pignataro, C. M. Schofield, M. Yue, N. L. Harrison, and P. A. Goldstein An Extrasynaptic GABAA Receptor Mediates Tonic Inhibition in Thalamic VB Neurons J Neurophysiol, December 1, 2005; 94(6): 4491 - 4501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Scimemi, A. Semyanov, G. Sperk, D. M. Kullmann, and M. C. Walker Multiple and Plastic Receptors Mediate Tonic GABAA Receptor Currents in the Hippocampus J. Neurosci., October 26, 2005; 25(43): 10016 - 10024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Keros and J. J. Hablitz Subtype-Specific GABA Transporter Antagonists Synergistically Modulate Phasic and Tonic GABAA Conductances in Rat Neocortex J Neurophysiol, September 1, 2005; 94(3): 2073 - 2085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Naylor, H. Liu, and C. G. Wasterlain Trafficking of GABAA Receptors, Loss of Inhibition, and a Mechanism for Pharmacoresistance in Status Epilepticus J. Neurosci., August 24, 2005; 25(34): 7724 - 7733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Mangan, C. Sun, M. Carpenter, H. P. Goodkin, W. Sieghart, and J. Kapur Cultured Hippocampal Pyramidal Neurons Express Two Kinds of GABAA Receptors Mol. Pharmacol., March 1, 2005; 67(3): 775 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Mody Aspects of the homeostaic plasticity of GABAA receptor-mediated inhibition J. Physiol., January 1, 2005; 562(1): 37 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Feng and R. L. Macdonald Multiple Actions of Propofol on {alpha}{beta}{gamma} and {alpha}{beta}{delta} GABAA Receptors Mol. Pharmacol., December 1, 2004; 66(6): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L Fisher The {alpha}1 and {alpha}6 subunit subtypes of the mammalian GABAA receptor confer distinct channel gating kinetics J. Physiol., December 1, 2004; 561(2): 433 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Bohme, H. Rabe, and H. Luddens Four Amino Acids in the {alpha} Subunits Determine the {gamma}-Aminobutyric Acid Sensitivities of GABAA Receptor Subtypes J. Biol. Chem., August 20, 2004; 279(34): 35193 - 35200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Boehm II, L. Peden, R. A. Harris, and Y. A. Blednov Deletion of the fyn-Kinase Gene Alters Sensitivity to GABAergic Drugs: Dependence on {beta}2/{beta}3 GABAA Receptor Subunits J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1154 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Minier and E. Sigel Positioning of the {alpha}-subunit isoforms confers a functional signature to {gamma}-aminobutyric acid type A receptors PNAS, May 18, 2004; 101(20): 7769 - 7774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carta, M. Mameli, and C. F. Valenzuela Alcohol Enhances GABAergic Transmission to Cerebellar Granule Cells via an Increase in Golgi Cell Excitability J. Neurosci., April 14, 2004; 24(15): 3746 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Stell, S. G. Brickley, C. Y. Tang, M. Farrant, and I. Mody Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by {delta} subunit-containing GABAA receptors PNAS, November 25, 2003; 100(24): 14439 - 14444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wei, N. Zhang, Z. Peng, C. R. Houser, and I. Mody Perisynaptic Localization of {delta} Subunit-Containing GABAA Receptors and Their Activation by GABA Spillover in the Mouse Dentate Gyrus J. Neurosci., November 19, 2003; 23(33): 10650 - 10661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Richerson and Y. Wu Dynamic Equilibrium of Neurotransmitter Transporters: Not Just for Reuptake Anymore J Neurophysiol, September 1, 2003; 90(3): 1363 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Engblom, F. F. Johansen, and U. Kristiansen Actions and Interactions of Extracellular Potassium and Kainate on Expression of 13 gamma -Aminobutyric Acid Type A Receptor Subunits in Cultured Mouse Cerebellar Granule Neurons J. Biol. Chem., May 2, 2003; 278(19): 16543 - 16550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wu, W. Wang, and G. B. Richerson Vigabatrin Induces Tonic Inhibition Via GABA Transporter Reversal Without Increasing Vesicular GABA Release J Neurophysiol, April 1, 2003; 89(4): 2021 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Kinney and W. J. Spain Synaptically Evoked GABA Transporter Currents in Neocortical Glia J Neurophysiol, December 1, 2002; 88(6): 2899 - 2908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Fisher Amiloride Inhibition of gamma -Aminobutyric AcidA Receptors Depends upon the alpha Subunit Subtype Mol. Pharmacol., June 1, 2002; 61(6): 1322 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Nusser and I. Mody Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells J Neurophysiol, May 1, 2002; 87(5): 2624 - 2628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Baufreton, M. Garret, S. Dovero, B. Dufy, B. Bioulac, and A. Taupignon Activation of GABAA Receptors in Subthalamic Neurons In Vitro: Properties of Native Receptors and Inhibition Mechanisms J Neurophysiol, July 1, 2001; 86(1): 75 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Bianchi, K. F. Haas, and R. L. Macdonald Structural Determinants of Fast Desensitization and Desensitization-Deactivation Coupling in GABAA Receptors J. Neurosci., February 15, 2001; 21(4): 1127 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Feigenspan, S. Gustincich, and E. Raviola Pharmacology of GABAA Receptors of Retinal Dopaminergic Neurons J Neurophysiol, October 1, 2000; 84(4): 1697 - 1707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Gibbs III, Y.-F. Zhang, M. D. Shumate, and D. A. Coulter Regionally Selective Blockade of GABAergic Inhibition by Zinc in the Thalamocortical System: Functional Significance J Neurophysiol, March 1, 2000; 83(3): 1510 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Banks and R. A. Pearce Kinetic Differences between Synaptic and Extrasynaptic GABAA Receptors in CA1 Pyramidal Cells J. Neurosci., February 1, 2000; 20(3): 937 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Mihalek, P. K. Banerjee, E. R. Korpi, J. J. Quinlan, L. L. Firestone, Z.-P. Mi, C. Lagenaur, V. Tretter, W. Sieghart, S. G. Anagnostaras, et al. Attenuated sensitivity to neuroactive steroids in gamma -aminobutyrate type A receptor delta subunit knockout mice PNAS, October 26, 1999; 96(22): 12905 - 12910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Neelands and R. L. Macdonald Incorporation of the pi Subunit into Functional gamma -Aminobutyric AcidA Receptors Mol. Pharmacol., September 1, 1999; 56(3): 598 - 610. [Abstract] [Full Text]
|
|
|
|
|
|
D. F. Owens, X. Liu, and A. R. Kriegstein Changing Properties of GABAA Receptor-Mediated Signaling During Early Neocortical Development J Neurophysiol, August 1, 1999; 82(2): 570 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sur, S. J. Farrar, J. Kerby, P. J. Whiting, J. R. Atack, and R. M. McKernan Preferential Coassembly of alpha 4 and delta Subunits of the gamma -Aminobutyric AcidA Receptor in Rat Thalamus Mol. Pharmacol., July 1, 1999; 56(1): 110 - 115. [Abstract] [Full Text]
|
|
|
|
|
|
E. I. Tietz, J. Kapur, and R. L. Macdonald Functional GABAA Receptor Heterogeneity of Acutely Dissociated Hippocampal CA1 Pyramidal Cells J Neurophysiol, April 1, 1999; 81(4): 1575 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kapur and R. L. Macdonald Postnatal Development of Hippocampal Dentate Granule Cell gamma -Aminobutyric AcidA Receptor Pharmacological Properties Mol. Pharmacol., March 1, 1999; 55(3): 444 - 452. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. A. Barnard, P. Skolnick, R. W. Olsen, H. Mohler, W. Sieghart, G. Biggio, C. Braestrup, A. N. Bateson, and S. Z. Langer International Union of Pharmacology. XV. Subtypes of gamma -Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Structure and Receptor Function Pharmacol. Rev., June 1, 1998; 50(2): 291 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Fisher and R. L. Macdonald The Role of an alpha Subtype M2-M3 His in Regulating Inhibition of GABAA Receptor Current by Zinc and Other Divalent Cations J. Neurosci., April 15, 1998; 18(8): 2944 - 2953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Nusser, W. Sieghart, and P. Somogyi Segregation of Different GABAA Receptors to Synaptic and Extrasynaptic Membranes of Cerebellar Granule Cells J. Neurosci., March 1, 1998; 18(5): 1693 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kapur and R. L. Macdonald Rapid Seizure-Induced Reduction of Benzodiazepine and Zn2+ Sensitivity of Hippocampal Dentate Granule Cell GABAA Receptors J. Neurosci., October 1, 1997; 17(19): 7532 - 7540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Fisher, J. Zhang, and R. L. Macdonald The Role of alpha 1 and alpha 6 Subtype Amino-Terminal Domains in Allosteric Regulation of gamma -Aminobutyric Acida Receptors Mol. Pharmacol., October 1, 1997; 52(4): 714 - 724. [Abstract] [Full Text]
|
|
|
|
|
|
R. Mäkelä, M. Uusi-Oukari, G. E. Homanics, J. J. Quinlan, L. L. Firestone, W. Wisden, and E. R. Korpi Cerebellar gamma -Aminobutyric Acid Type A Receptors: Pharmacological Subtypes Revealed by Mutant Mouse Lines Mol. Pharmacol., September 1, 1997; 52(3): 380 - 388. [Abstract] [Full Text]
|
|
|
|
|
|
P. J. Whiting, G. McAllister, D. Vassilatis, T. P. Bonnert, R. P. Heavens, D. W. Smith, L. Hewson, R. O'Donnell, M. R. Rigby, D. J. S. Sirinathsinghji, et al. Neuronally Restricted RNA Splicing Regulates the Expression of a Novel GABAA Receptor Subunit Conferring Atypical Functional Properties J. Neurosci., July 1, 1997; 17(13): 5027 - 5037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Homanics, C. Ferguson, J. J. Quinlan, J. Daggett, K. Snyder, C. Lagenaur, Z.-P. Mi, X.-H. Wang, D. R. Grayson, and L. L. Firestone Gene Knockout of the alpha 6 Subunit of the gamma -Aminobutyric Acid Type A Receptor: Lack of Effect on Responses to Ethanol, Pentobarbital, and General Anesthetics Mol. Pharmacol., April 1, 1997; 51(4): 588 - 596. [Abstract] [Full Text]
|
|
|
|
|
|
A. Jones, E. R. Korpi, R. M. McKernan, R. Pelz, Z. Nusser, R. Makela, J. R. Mellor, S. Pollard, S. Bahn, F. A. Stephenson, et al. Ligand-Gated Ion Channel Subunit Partnerships: GABAA Receptor alpha 6 Subunit Gene Inactivation Inhibits delta Subunit Expression J. Neurosci., February 15, 1997; 17(4): 1350 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Saxena, T. R. Neelands, and R. L. Macdonald Contrasting Actions of Lanthanum on Different Recombinant gamma -Aminobutyric Acid Receptor Isoforms Expressed in L929 Fibroblasts Mol. Pharmacol., February 1, 1997; 51(2): 328 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Zhu, J. F. Wang, K. E. Krueger, and S. Vicini delta Subunit Inhibits Neurosteroid Modulation of GABAA Receptors J. Neurosci., November 1, 1996; 16(21): 6648 - 6656. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
