QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thio, L. L. Articles by Zorumski, C. F. Search for Related Content PubMed PubMed Citation Articles by Thio, L. L. Articles by Zorumski, C. F.

 Previous Article  |  Next Article 

Journal of Neuroscience, Vol 11, 3430-3441, Copyright © 1991 by Society for Neuroscience

ARTICLE

Characterization of quisqualate receptor desensitization in cultured postnatal rat hippocampal neurons

LL Thio, DB Clifford and CF Zorumski
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.

The quisqualate class of glutamate receptors is thought to play an important role in excitatory synaptic transmission, synaptic plasticity, and neuronal death. Since desensitization is a prominent feature of the responses mediated by this class of receptors, we have characterized the rapidly desensitizing quisqualate response in cultured postnatal rat hippocampal neurons using the whole-cell patch- clamp technique. Quisqualate and its structural analogs elicit a peak current that rapidly decays to a steady-state level. In contrast, currents induced by kainate, NMDA, and their structural analogs exhibit either no decay or a much slower decay. The biophysical and pharmacological properties of the peak and steady-state quisqualate currents indicate that both are mediated by an ionotropic quisqualate receptor. Quisqualate currents desensitized monoexponentially by approximately 70% with a time constant near 80 msec. Both the rate and percentage of desensitization showed slight voltage dependence and were concentration dependent, reaching maximal values at saturation. Additionally, the overlap of the dose-response curves for activation of the steady-state current and desensitization of the peak current by a conditioning dose suggests that the two processes are related. Furthermore, desensitizing quisqualate currents were observed when Ca2+, Mg2+, Na+, K+, and Cl- were removed from the extracellular solution or their concentrations greatly reduced. These results suggest that the decline in the response is not caused by a simple open channel block mechanism. Despite the lack of desensitization by kainate, our observations are consistent with the hypothesis that quisqualate and kainate act at a single receptor-channel complex. Kainate and quisqualate appeared to interact competitively when applied simultaneously and noncompetitively when quisqualate was applied first. In addition, saturating doses of quisqualate and kainate gave steady- state currents of equal amplitude in neurons treated with the lectin WGA, an inhibitor of quisqualate receptor desensitization.

This article has been cited by other articles:

				D. F. Covey, D. Nathan, M. Kalkbrenner, K. R. Nilsson, Y. Hu, C. F. Zorumski, and A. S. Evers Enantioselectivity of Pregnanolone-Induced gamma -Aminobutyric AcidA Receptor Modulation and Anesthesia J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 1009 - 1016. [Abstract] [Full Text]

				G. O. Hjelmstad, J. T. R. Isaac, R. A. Nicoll, and R. C. Malenka Lack of AMPA Receptor Desensitization During Basal Synaptic Transmission in the Hippocampal Slice J Neurophysiol, June 1, 1999; 81(6): 3096 - 3099. [Abstract] [Full Text] [PDF]

				I. Mano, Y. Lamed, and V. I. Teichberg A Venus Flytrap Mechanism for Activation and Desensitization of alpha -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptors J. Biol. Chem., June 28, 1996; 271(26): 15299 - 15302. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help