| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
J Neurophysiol (April 1, 2003). 10.1152/jn.00856.2002
Submitted on Submitted 25 September 2002; accepted in final form 26 December
2002
1Departments of Neurology, and 2Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520; and 3Veteran's Affairs Medical Center, West Haven, Connecticut 06516
Wu, Yuanming,
Wengang Wang, and
George B. Richerson.
Vigabatrin Induces Tonic Inhibition Via GABA Transporter Reversal
Without Increasing Vesicular GABA Release. J. Neurophysiol. 89: 2021-2034, 2003. Two forms of
GABAergic inhibition coexist: fast synaptic neurotransmission and tonic
activation of GABA receptors due to ambient GABA. The mechanisms
regulating ambient GABA have not been well defined. Here we examined
the role of the GABA transporter in the increase in ambient [GABA]
induced by the anticonvulsant vigabatrin. Pretreatment of cultured rat
hippocampal neurons with vigabatrin (100 µM) for 2-5 days led to a
large increase in ambient [GABA] that was measured as the change in
holding current induced by bicuculline during patch-clamp recordings.
In contrast, there was a decrease in the frequency of spontaneous
miniature inhibitory postsynaptic currents mIPSCs with no change in
their amplitude distribution, and a decrease in the magnitude of IPSCs
evoked by presynaptic stimulation during paired recordings. The
increase in ambient [GABA] was not prevented by blockade of vesicular
GABA release with tetanus toxin or removal of extracellular calcium. During perforated patch recordings, the increase in ambient [GABA] was prevented by blocking the GABA transporter, indicating that the
GABA transporter was continuously operating in reverse and releasing
GABA. In contrast, blocking the GABA transporter increased ambient
[GABA] during whole cell patch-clamp recordings unless GABA and
Na+ were added to the recording electrode
solution, indicating that whole cell recordings can lead to erroneous
conclusions about the role of the GABA transporter in control of
ambient GABA. We conclude that the equilibrium for the GABA transporter
is a major determinant of ambient [GABA] and tonic GABAergic
inhibition. We propose that fast GABAergic neurotransmission and tonic
inhibition can be independently modified and play complementary roles
in control of neuronal excitability.
This article has been cited by other articles:
|
|
 |
|
  O. A. Sergeeva, W. Fleischer, A. N. Chepkova, U. Warskulat, D. Haussinger, M. Siebler, and H. L. Haas GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition J. Physiol., December 1, 2007; 585(2): 539 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Glykys and I. Mody The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus J. Physiol., August 1, 2007; 582(3): 1163 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wu, W. Wang, and G. B. Richerson The Transmembrane Sodium Gradient Influences Ambient GABA Concentration by Altering the Equilibrium of GABA Transporters J Neurophysiol, November 1, 2006; 96(5): 2425 - 2436. [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]
|
|
|
|
|
|
V. Y. Cheng, L. J. Martin, E. M. Elliott, J. H. Kim, H. T. J. Mount, F. A. Taverna, J. C. Roder, J. F. MacDonald, A. Bhambri, N. Collinson, et al. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J. Neurosci., April 5, 2006; 26(14): 3713 - 3720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Remy and H. Beck Molecular and cellular mechanisms of pharmacoresistance in epilepsy Brain, January 1, 2006; 129(1): 18 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Kinney GAT-3 Transporters Regulate Inhibition in the Neocortex J Neurophysiol, December 1, 2005; 94(6): 4533 - 4537. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
V. B. Caraiscos, J. G. Newell, K. E. You-Ten, E. M. Elliott, T. W. Rosahl, K. A. Wafford, J. F. MacDonald, and B. A. Orser Selective Enhancement of Tonic GABAergic Inhibition in Murine Hippocampal Neurons by Low Concentrations of the Volatile Anesthetic Isoflurane J. Neurosci., September 29, 2004; 24(39): 8454 - 8458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Mycielska and M. B. A. Djamgoz Citrate transport in the human prostate epithelial PNT2-C2 cell line: electrophysiological analyses J. Physiol., September 15, 2004; 559(3): 821 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Caraiscos, E. M. Elliott, K. E. You-Ten, V. Y. Cheng, D. Belelli, J. G. Newell, M. F. Jackson, J. J. Lambert, T. W. Rosahl, K. A. Wafford, et al. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by {alpha}5 subunit-containing {gamma}-aminobutyric acid type A receptors PNAS, March 9, 2004; 101(10): 3662 - 3667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Costa, G. Leone, E. Saulle, F. Pisani, G. Bernardi, and P. Calabresi Coactivation of GABAA and GABAB Receptor Results in Neuroprotection During In Vitro Ischemia Stroke, February 1, 2004; 35(2): 596 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Axmacher, M. Stemmler, D. Engel, A. Draguhn, and R. Ritz Transmitter Metabolism as a Mechanism of Synaptic Plasticity: A Modeling Study J Neurophysiol, January 1, 2004; 91(1): 25 - 39. [Abstract] [Full Text]
|
|
|
|
|
|
M. T. Bianchi and R. L. Macdonald Neurosteroids Shift Partial Agonist Activation of GABAA Receptor Channels from Low- to High-Efficacy Gating Patterns J. Neurosci., November 26, 2003; 23(34): 10934 - 10943. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
