Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Click Me!

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 11 October 1991:
Vol. 254. no. 5029, pp. 288 - 290
DOI: 10.1126/science.1681589

Articles

Science, Vol 254, Issue 5029, 288-290
Copyright © 1991 by American Association for the Advancement of Science


articles

Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam

CM Tang, QY Shi, A Katchman, and G Lynch

Department of Neurology, University of Pennsylvania, Philadelphia.

It is generally accepted that glutamate serves as the neurotransmitter at most excitatory synapses in the mammalian central nervous system (CNS). Synaptic release of glutamate may trigger a fast and a slow excitatory postsynaptic current (EPSC). The slow EPSC is mediated by N-methyl-D-aspartate (NMDA) receptor channels, whereas the fast EPSC is mediated by non-NMDA receptor channels. The nootropic agent aniracetam selectively and reversibly slows the desensitization kinetics of non-NMDA channels and lengthens their single-channel open times. Antiracetam also modulates the kinetics of the fast EPSC in a manner that mirrors its action on the kinetics of the non-NMDA channels. These results support the hypothesis that the properties of the non-NMDA glutamate channels rather than the rate of neurotransmitter clearance are the primary determinants of the kinetics of the fast EPSC in the mammalian CNS.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mechanism of Positive Allosteric Modulators Acting on AMPA Receptors.
R. Jin, S. Clark, A. M. Weeks, J. T. Dudman, E. Gouaux, and K. M. Partin (2005)
J. Neurosci. 25, 9027-9036
   Abstract »    Full Text »    PDF »
NEUROPHARMACOKINETICS OF A NEW {alpha}-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC ACID (AMPA) MODULATOR, S18986 [(S)-2,3-DIHYDRO-[3,4]CYCLOPENTANO-1,2,4-BENZOTHIADIAZINE-1,1-DIOXIDE], IN THE RAT.
F. Bourasset, K. Bernard, C. Munoz, P. Genissel, and J.-M. Scherrmann (2005)
Drug Metab. Dispos. 33, 1137-1143
   Abstract »    Full Text »    PDF »
Nootropic Agents Enhance the Recruitment of Fast GABAA Inhibition in Rat Neocortex.
D. S.F. Ling and L. S. Benardo (2005)
Cereb Cortex 15, 921-928
   Abstract »    Full Text »    PDF »
The Mechanism of Action of Aniracetam at Synaptic {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors: Indirect and Direct Effects on Desensitization.
J. J. Lawrence, S. Brenowitz, and L. O. Trussell (2003)
Mol. Pharmacol. 64, 269-278
   Abstract »    Full Text »    PDF »
Long-Term Potentiation Alters the Modulator Pharmacology of AMPA-Type Glutamate Receptors.
B. Lin, F. A. Brucher, L. L. Colgin, and G. Lynch (2002)
J Neurophysiol 87, 2790-2800
   Abstract »    Full Text »    PDF »
Mechanisms Shaping Fast Excitatory Postsynaptic Currents in the Central Nervous System.
M. I. Glavinovic (2002)
Neural Comput. 14, 1-19
   Abstract »    Full Text »    PDF »
Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter.
R. R. Gainetdinov, A. R. Mohn, L. M. Bohn, and M. G. Caron (2001)
PNAS 98, 11047-11054
   Abstract »    Full Text »    PDF »
Effect of FK960, a Putative Cognitive Enhancer, on Synaptic Transmission in CA1 Neurons of Rat Hippocampus.
J. P. Hodgkiss and J. S. Kelly (2001)
J. Pharmacol. Exp. Ther. 297, 620-628
   Abstract »    Full Text »
Nootropic Drug Modulation of Neuronal Nicotinic Acetylcholine Receptors in Rat Cortical Neurons.
X. Zhao, A. Kuryatov, J. M. Lindstrom, J. Z. Yeh, and T. Narahashi (2001)
Mol. Pharmacol. 59, 674-683
   Abstract »    Full Text »
Effects of the Potent Ampakine CX614 on Hippocampal and Recombinant AMPA Receptors: Interactions with Cyclothiazide and GYKI 52466.
A. C. Arai, M. Kessler, G. Rogers, and G. Lynch (2000)
Mol. Pharmacol. 58, 802-813
   Abstract »    Full Text »
Activity of Putative Cognition Enhancers in Kynurenate Test Performed with Human Neocortex Slices.
A. Pittaluga, R. Pattarini, G. C. Andrioli, C. Viola, C. Munari, and M. Raiteri (1999)
J. Pharmacol. Exp. Ther. 290, 423-428
   Abstract »    Full Text »
Endogenous Neurotrophin-3 Regulates Short-Term Plasticity at Lateral Perforant Path-Granule Cell Synapses.
M. Kokaia, F. Asztely, K. Olofsdotter, C. B. Sindreu, D. M. Kullmann, and O. Lindvall (1998)
J. Neurosci. 18, 8730-8739
   Abstract »    Full Text »    PDF »
Presynaptic Modulation of Synaptic Transmission and Plasticity by Brain-Derived Neurotrophic Factor in the Developing Hippocampus.
W. Gottschalk, L. D. Pozzo-Miller, A. Figurov, and B. Lu (1998)
J. Neurosci. 18, 6830-6839
   Abstract »    Full Text »    PDF »
Nefiracetam Modulates Acetylcholine Receptor Currents via Two Different Signal Transduction Pathways.
T. Nishizaki, T. Matsuoka, T. Nomura, K. Sumikawa, T. Shiotani, S. Watabe, and M. Yoshii (1998)
Mol. Pharmacol. 53, 1-5
   Abstract »    Full Text »
Mechanisms of Potentiation by Calcium-Calmodulin Kinase II of Postsynaptic Sensitivity in Rat Hippocampal CA1 Neurons.
A. M. Shirke and R. Malinow (1997)
J Neurophysiol 78, 2682-2692
   Abstract »    Full Text »    PDF »
A Novel Allosteric Potentiator of AMPA Receptors: 4-[2-(Phenylsulfonylamino)ethylthio]-2,6-Difluoro-Phenoxyacetamide.
M. Sekiguchi, M. W. Fleck, M. L. Mayer, J. Takeo, Y. Chiba, S. Yamashita, and K. Wada (1997)
J. Neurosci. 17, 5760-5771
   Abstract »    Full Text »    PDF »
Direct Measurement of AMPA Receptor Desensitization Induced by Glutamatergic Synaptic Transmission.
T. Otis, S. Zhang, and L. O. Trussell (1996)
J. Neurosci. 16, 7496-7504
   Abstract »    Full Text »    PDF »
AMPA Receptor Flip/Flop Mutants Affecting Deactivation, Desensitization, and Modulation by Cyclothiazide, Aniracetam, and Thiocyanate.
K. M. Partin, M. W. Fleck, and M. L. Mayer (1996)
J. Neurosci. 16, 6634-6647
   Abstract »    Full Text »    PDF »
The treatment of Alzheimer's disease.
N.H.P. Allen and A. Burns (1995)
J Psychopharmacol 9, 43-56
   PDF »
Aniracetam improves behavioural responses and facilitates signal transduction in the rat brain.
C. Ventra, M. Grimaldi, O. Meucci, A. Scorziello, A. Apicella, E. Filetti, A. Marino, and G. Schettini (1994)
J Psychopharmacol 8, 109-117
   Abstract »    PDF »
Bench to bedside: the glutamate connection.
D. Choi (1992)
Science 258, 241-243
   PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)