Antagonists of NMDA-Activated Current in Cortical Neurons: Competition with Glycine and Blockade of Open Channels
There is increasing evidence that ion channels activated by L-glutamate underlie rapid excitatory synaptic transmission throughout the vertebrate central nervous system (Mayer and Westbrook, 1987) Nearly 30 years ago, glutamate was found to depolarize neurons in most areas of the brain and spinal cord (Hayashi, 1954; Curtis et al. 1960; Krnjevic and Phillis, 1963) but it was not until pharmacological experiments revealed the presence of several distinct receptors (Watkins and Olverman, 1987) for glutamate that significant progress was made toward understanding the mechanisms of glutamate excitation. Over the past ten years, the discovery of selective agonists and antagonists has played a major role in defining the subtypes of glutamate receptors (Dingledine et al. 1988) and recent studies (Jahr and Stevens, 1987; Ascher et al., 1988; Cull-Candy et al., 1988) of whole-cell and single channel currents using the patch clamp technique (Hamill et al., 1981) have begun to provide information about the channels gated by glutamate receptors.
KeywordsNMDA Receptor Kynurenic Acid Excitatory Amino Acid Receptor Glycine Site Unpublished Experiment
Unable to display preview. Download preview PDF.
- R. Dingledine, L. M. Boland, N. L. Chamberlin, K. Kawasaki, N. W. Kleckner, S. F. Traynelis, and T. A. Verdoorn, Amino acid receptors and uptake systems in the mammalian central nervous system, CRC Crit. Rev. Neurobiol. 4: 1 (1988).Google Scholar
- J. Elguero, C. Marzin, A. R. Katritzky, and P. Linda, The tautomerism of heterocycles, Adv. Heterocyclic Chem. Supp. 1 (1976).Google Scholar
- W. Haefely, E. Kyburz, M. Gerecke, and M. Mohler, Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure activity relationships of their agonists and antagonists, Adv. Drug Res. 14: 165 (1985).Google Scholar
- M. L. Mayer, G. L. Westbrook, and L. Vyklicky, Jr., Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J. Neurophysiol. 60: 65 (1988)Google Scholar