| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Neuroscience |
ß subunit GABAA receptors on rat hippocampal pyramidal neurons
1 Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Extrasynaptic GABAA receptors that are tonically activated by ambient GABA are important for controlling neuronal excitability. In hippocampal pyramidal neurons, the subunit composition of these extrasynaptic receptors may include 
5ß
and/or 4ß
subunits. Our present studies reveal that a component of the tonic current in the hippocampus is highly sensitive to inhibition by Zn2+. This component is probably not mediated by either 5ß or 4ß receptors, but might be explained by the presence of ß isoforms. Using patch-clamp recording from pyramidal neurons, a small tonic current measured in the absence of exogenous GABA exhibited both high and low sensitivity to Zn2+ inhibition (IC50 values, 1.89 and 223 µM, respectively). Using low nanomolar and micromolar GABA concentrations to replicate tonic currents, we identified two components that are mediated by benzodiazepine-sensitive and -insensitive receptors. The latter indicated that extrasynaptic GABAA receptors exist that are devoid of 2 subunits. To distinguish whether the benzodiazepine-insensitive receptors were ß or ß isoforms, we used single-channel recording. Expressing recombinant 1ß32, 5ß32, 4ß3 and 1ß3 receptors in human embryonic kidney (HEK) or mouse fibroblast (Ltk) cells, revealed similar openings with high main conductances (
25–28 pS) for 2 or subunit-containing receptors whereas ß receptors were characterized by a lower main conductance state (11 pS). Recording from pyramidal cell somata revealed a similar range of channel conductances, indicative of a mixture of GABAA receptors in the extrasynaptic membrane. The lowest conductance state (11 pS) was the most sensitive to Zn2+ inhibition in accord with the presence of ß receptors. This receptor type is estimated to account for up to 10% of all extrasynaptic GABAA receptors on hippocampal pyramidal neurons.
(Received 26 July 2006;
accepted after revision 4 October 2006;
first published online 12 October 2006)
Corresponding author T. G. Smart: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.smart{at}ucl.ac.uk
This article has been cited by other articles:
|
|
 |
|
  J. Glykys, E. O. Mann, and I. Mody Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus? J. Neurosci., February 6, 2008; 28(6): 1421 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Ade, M. J. Janssen, P. I. Ortinski, and S. Vicini Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons J. Neurosci., January 30, 2008; 28(5): 1185 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Palma, C. Roseti, F. Maiolino, S. Fucile, K. Martinello, M. Mazzuferi, E. Aronica, M. Manfredi, V. Esposito, G. Cantore, et al. GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA "phasic" receptors PNAS, December 26, 2007; 104(52): 20944 - 20948. [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]
|
|
|
|
|
|
F. F. Trigo, M. Chat, and A. Marty Enhancement of GABA Release through Endogenous Activation of Axonal GABAA Receptors in Juvenile Cerebellum J. Neurosci., November 14, 2007; 27(46): 12452 - 12463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-H. Qi, M. Song, M. J. Wallace, D. Wang, P. M. Newton, T. McMahon, W.-H. Chou, C. Zhang, K. M. Shokat, and R. O. Messing Protein Kinase C{epsilon} Regulates {gamma}-Aminobutyrate Type A Receptor Sensitivity to Ethanol and Benzodiazepines through Phosphorylation of {gamma}2 Subunits J. Biol. Chem., November 9, 2007; 282(45): 33052 - 33063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zhang, W. Wei, I. Mody, and C. R. Houser Altered Localization of GABAA Receptor Subunits on Dentate Granule Cell Dendrites Influences Tonic and Phasic Inhibition in a Mouse Model of Epilepsy J. Neurosci., July 11, 2007; 27(28): 7520 - 7531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mizokami, T. Kanematsu, H. Ishibashi, T. Yamaguchi, I. Tanida, K. Takenaka, K. I. Nakayama, K. Fukami, T. Takenawa, E. Kominami, et al. Phosholipase C-Related Inactive Protein Is Involved in Trafficking of {gamma}2 Subunit-Containing GABAA Receptors to the Cell Surface J. Neurosci., February 14, 2007; 27(7): 1692 - 1701. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
