Antagonists of NMDA-Activated Current in Cortical Neurons: Competition with Glycine and Blockade of Open Channels

Abstract

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.

This work was supported by the Harvard University Society of Fellows, the Esther A. and Joseph Klingenstein Fund and by grants to Bruce P. Bean from the National Institutes of Health (HL-35034), the Culpeper Foundation and the Rita Allen Foundation. I am grateful to Bruce Bean for many helpful discussions and for support.