 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, November 1, 2000, 20(21):7914-7921
Slow Desensitization Regulates the Availability of Synaptic GABAA Receptors
Linda S. Overstreet1, Mathew V. Jones2, and Gary L. Westbrook1 1 Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, and 2 Department of Physiology, University of Wisconsin-Madison, Madison, Wisconsin 53706
At central synapses, a large and fast spike of neurotransmitter efficiently activates postsynaptic receptors. However, low concentrations of transmitter can escape the cleft and activate presynaptic and postsynaptic receptors. We report here that low concentrations of GABA reduce IPSCs in hippocampal neurons by preferentially desensitizing rather than opening GABAA channels. GABA transporter blockade also caused desensitization by locally elevating GABA to ~1 µM. Recovery of the IPSC required several seconds, mimicking recovery of the channel from slow desensitization. These results indicate that low levels of GABA can regulate the amplitude of IPSCs by producing a slow form of receptor desensitization. Accumulation of channels in this absorbing state allows GABAA receptors to detect even a few molecules of GABA in the synaptic cleft.
Key words: synaptic inhibition; desensitization; mIPSC; hippocampus; GABA transporters; ligand-gated ion channel; uptake blocker; postsynaptic
Copyright © 2000 Society for Neuroscience 0270-6474/00/20217914-08$05.00/0
This article has been cited by other articles:
C. P. Ford, P. E. M. Phillips, and J. T. Williams
The Time Course of Dopamine Transmission in the Ventral Tegmental Area
J. Neurosci., October 21, 2009; 29(42): 13344 - 13352.
[Abstract] [Full Text] [PDF]
N. Maggio and M. Segal
Differential Corticosteroid Modulation of Inhibitory Synaptic Currents in the Dorsal and Ventral Hippocampus
J. Neurosci., March 4, 2009; 29(9): 2857 - 2866.
[Abstract] [Full Text] [PDF]
G. Gonzalez-Burgos, D. C. Rotaru, A. V. Zaitsev, N. V. Povysheva, and D. A. Lewis
GABA Transporter GAT1 Prevents Spillover at Proximal and Distal GABA Synapses Onto Primate Prefrontal Cortex Neurons
J Neurophysiol, February 1, 2009; 101(2): 533 - 547.
[Abstract] [Full Text] [PDF]
K. Kirmse, A. Dvorzhak, S. Kirischuk, and R. Grantyn
GABA transporter 1 tunes GABAergic synaptic transmission at output neurons of the mouse neostriatum
J. Physiol., December 1, 2008; 586(23): 5665 - 5678.
[Abstract] [Full Text] [PDF]
J. Baufreton and M. D. Bevan
D2-like dopamine receptor-mediated modulation of activity-dependent plasticity at GABAergic synapses in the subthalamic nucleus
J. Physiol., April 15, 2008; 586(8): 2121 - 2142.
[Abstract] [Full Text] [PDF]
H. Sun, X.-Q. Hu, M. B. Emerit, J. C. Schoenebeck, C. E. Kimmel, R. W. Peoples, A. Miko, and L. Zhang
Modulation of 5-HT3 receptor desensitization by the light chain of microtubule-associated protein 1B expressed in HEK 293 cells
J. Physiol., February 1, 2008; 586(3): 751 - 762.
[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]
C. M. Schofield and J. R. Huguenard
GABA Affinity Shapes IPSCs in Thalamic Nuclei
J. Neurosci., July 25, 2007; 27(30): 7954 - 7962.
[Abstract] [Full Text] [PDF]
S. H. R. Oliet, D. V. Baimoukhametova, R. Piet, and J. S. Bains
Retrograde Regulation of GABA Transmission by the Tonic Release of Oxytocin and Endocannabinoids Governs Postsynaptic Firing
J. Neurosci., February 7, 2007; 27(6): 1325 - 1333.
[Abstract] [Full Text] [PDF]
A. H. Lagrange, E. J. Botzolakis, and R. L. Macdonald
Enhanced macroscopic desensitization shapes the response of {alpha}4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA
J. Physiol., February 1, 2007; 578(3): 655 - 676.
[Abstract] [Full Text] [PDF]
C. Hull, G.-L. Li, and H. von Gersdorff
GABA transporters regulate a standing GABAC receptor-mediated current at a retinal presynaptic terminal.
J. Neurosci., June 28, 2006; 26(26): 6979 - 6984.
[Abstract] [Full Text] [PDF]
K. Kirmse and S. Kirischuk
Ambient GABA constrains the strength of GABAergic synapses at Cajal-Retzius cells in the developing visual cortex.
J. Neurosci., April 19, 2006; 26(16): 4216 - 4227.
[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]
A. J. Boileau, R. A. Pearce, and C. Czajkowski
Tandem Subunits Effectively Constrain GABAA Receptor Stoichiometry and Recapitulate Receptor Kinetics But Are Insensitive to GABAA Receptor-Associated Protein
J. Neurosci., December 7, 2005; 25(49): 11219 - 11230.
[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]
N. E. Hallworth and M. D. Bevan
Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABAA and GABAB Receptors
J. Neurosci., July 6, 2005; 25(27): 6304 - 6315.
[Abstract] [Full Text] [PDF]
C.-S. Chiu, S. Brickley, K. Jensen, A. Southwell, S. Mckinney, S. Cull-Candy, I. Mody, and H. A. Lester
GABA Transporter Deficiency Causes Tremor, Ataxia, Nervousness, and Increased GABA-Induced Tonic Conductance in Cerebellum
J. Neurosci., March 23, 2005; 25(12): 3234 - 3245.
[Abstract] [Full Text] [PDF]
N. J Allen and D. Attwell
The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the juvenile rat hippocampus
J. Physiol., December 1, 2004; 561(2): 485 - 498.
[Abstract] [Full Text] [PDF]
E. M. Petrini, I. Marchionni, P. Zacchi, W. Sieghart, and E. Cherubini
Clustering of Extrasynaptic GABAA Receptors Modulates Tonic Inhibition in Cultured Hippocampal Neurons
J. Biol. Chem., October 29, 2004; 279(44): 45833 - 45843.
[Abstract] [Full Text] [PDF]
H.-J. Feng, M. T. Bianchi, and R. L. Macdonald
Pentobarbital Differentially Modulates {alpha}1{beta}3{delta} and {alpha}1{beta}3{gamma}2L GABAA Receptor Currents
Mol. Pharmacol., October 1, 2004; 66(4): 988 - 1003.
[Abstract] [Full Text] [PDF]
S. Sipila, K. Huttu, J. Voipio, and K. Kaila
GABA Uptake via GABA Transporter-1 Modulates GABAergic Transmission in the Immature Hippocampus
J. Neurosci., June 30, 2004; 24(26): 5877 - 5880.
[Abstract] [Full Text] [PDF]
D. V. Baimoukhametova, S. A. Hewitt, C. A. Sank, and J. S. Bains
Dopamine Modulates Use-Dependent Plasticity of Inhibitory Synapses
J. Neurosci., June 2, 2004; 24(22): 5162 - 5171.
[Abstract] [Full Text] [PDF]
A. C. Hall, K. C. Rowan, R. J. N. Stevens, J. C. Kelley, and N. L. Harrison
The Effects of Isoflurane on Desensitized Wild-Type and {alpha}1(S270H) {gamma}-Aminobutyric Acid Type A Receptors
Anesth. Analg., May 1, 2004; 98(5): 1297 - 1304.
[Abstract] [Full Text] [PDF]
N. J. Allen, D. J. Rossi, and D. Attwell
Sequential Release of GABA by Exocytosis and Reversed Uptake Leads to Neuronal Swelling in Simulated Ischemia of Hippocampal Slices
J. Neurosci., April 14, 2004; 24(15): 3837 - 3849.
[Abstract] [Full Text] [PDF]
K. Jensen, C.-S. Chiu, I. Sokolova, H. A. Lester, and I. Mody
GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAA Versus GABAB Receptors in the Hippocampus
J Neurophysiol, October 1, 2003; 90(4): 2690 - 2701.
[Abstract] [Full Text] [PDF]
E. M. Petrini, P. Zacchi, A. Barberis, J. W. Mozrzymas, and E. Cherubini
Declusterization of GABAA Receptors Affects the Kinetic Properties of GABAergic Currents in Cultured Hippocampal Neurons
J. Biol. Chem., April 25, 2003; 278(18): 16271 - 16279.
[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]
L. S. Overstreet and G. L. Westbrook
Synapse Density Regulates Independence at Unitary Inhibitory Synapses
J. Neurosci., April 1, 2003; 23(7): 2618 - 2626.
[Abstract] [Full Text] [PDF]
G. Tamas, A. L. A. Simon, and J. Szabadics
Identified Sources and Targets of Slow Inhibition in the Neocortex
Science, March 21, 2003; 299(5614): 1902 - 1905.
[Abstract] [Full Text] [PDF]
J. W. Mozrzymas, A. Barberis, K. Mercik, and E. D. Zarnowska
Binding Sites, Singly Bound States, and Conformation Coupling Shape GABA-Evoked Currents
J Neurophysiol, February 1, 2003; 89(2): 871 - 883.
[Abstract] [Full Text] [PDF]
S. Lei and C. J McBain
GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons
J. Physiol., January 15, 2003; 546(2): 439 - 453.
[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]
P. M. Baker, P. S. Pennefather, B. A. Orser, and F. K. Skinner
Disruption of Coherent Oscillations in Inhibitory Networks With Anesthetics: Role of GABAA Receptor Desensitization
J Neurophysiol, November 1, 2002; 88(5): 2821 - 2833.
[Abstract] [Full Text] [PDF]
M. Scheller and S. A. Forman
Coupled and Uncoupled Gating and Desensitization Effects by Pore Domain Mutations in GABAA Receptors
J. Neurosci., October 1, 2002; 22(19): 8411 - 8421.
[Abstract] [Full Text] [PDF]
P. Telgkamp and I. M. Raman
Depression of Inhibitory Synaptic Transmission between Purkinje Cells and Neurons of the Cerebellar Nuclei
J. Neurosci., October 1, 2002; 22(19): 8447 - 8457.
[Abstract] [Full Text] [PDF]
M. T Bianchi and R. L Macdonald
Slow phases of GABAA receptor desensitization: structural determinants and possible relevance for synaptic function
J. Physiol., October 1, 2002; 544(1): 3 - 18.
[Abstract] [Full Text] [PDF]
Y. Chang, E. Ghansah, Y. Chen, J. Ye, and D. S. Weiss
Desensitization Mechanism of GABA Receptors Revealed by Single Oocyte Binding and Receptor Function
J. Neurosci., September 15, 2002; 22(18): 7982 - 7990.
[Abstract] [Full Text] [PDF]
J. G. Newell and S. M. J. Dunn
Functional Consequences of the Loss of High Affinity Agonist Binding to gamma -Aminobutyric Acid Type A Receptors. IMPLICATIONS FOR RECEPTOR DESENSITIZATION
J. Biol. Chem., June 7, 2002; 277(24): 21423 - 21430.
[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]
T. Klausberger, J. D. B. Roberts, and P. Somogyi
Cell Type- and Input-Specific Differences in the Number and Subtypes of Synaptic GABAA Receptors in the Hippocampus
J. Neurosci., April 1, 2002; 22(7): 2513 - 2521.
[Abstract] [Full Text] [PDF]
A. V. Buhler and T. V. Dunwiddie
alpha 7 Nicotinic Acetylcholine Receptors on GABAergic Interneurons Evoke Dendritic and Somatic Inhibition of Hippocampal Neurons
J Neurophysiol, January 1, 2002; 87(1): 548 - 557.
[Abstract] [Full Text] [PDF]
Z. Mtchedlishvili, E. H Bertram, and J. Kapur
Diminished allopregnanolone enhancement of GABAA receptor currents in a rat model of chronic temporal lobe epilepsy
J. Physiol., December 1, 2001; 537(2): 453 - 465.
[Abstract] [Full Text] [PDF]
P. M. Burkat, J. Yang, and K. J. Gingrich
Dominant Gating Governing Transient GABAA Receptor Activity: A First Latency and Po/o Analysis
J. Neurosci., September 15, 2001; 21(18): 7026 - 7036.
[Abstract] [Full Text] [PDF]
D. Engel, I. Pahner, K. Schulze, C. Frahm, H. Jarry, G. Ahnert-Hilger, and A. Draguhn
Plasticity of rat central inhibitory synapses through GABA metabolism
J. Physiol., September 1, 2001; 535(2): 473 - 482.
[Abstract] [Full Text] [PDF]
L. S. Overstreet and G. L. Westbrook
Paradoxical Reduction of Synaptic Inhibition by Vigabatrin
J Neurophysiol, August 1, 2001; 86(2): 596 - 603.
[Abstract] [Full Text] [PDF]
J. D. Hunter and J. G. Milton
Synaptic Heterogeneity and Stimulus-Induced Modulation of Depression in Central Synapses
J. Neurosci., August 1, 2001; 21(15): 5781 - 5793.
[Abstract] [Full Text] [PDF]
J. R. Mellor and A. D. Randall
Synaptically Released Neurotransmitter Fails to Desensitize Postsynaptic GABAA Receptors in Cerebellar Cultures
J Neurophysiol, May 1, 2001; 85(5): 1847 - 1857.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|