Experiments on the action of
glutamate on mammalian and amphibian nervous systems started back in the 1950s but decades passed before it became widely accepted that
glutamate was the major excitatory neurotransmitter in the CNS. The pace of research greatly accelerated in the 1980s when selective ligands that identified
glutamate receptor subtypes became widely available, and voltage clamp techniques, coupled with rapid perfusion, began to resolve the unique functional properties of what cloning subsequently revealed to be a large family of
receptors with numerous subtypes. More recently the power of X-ray crystallography and cryo-EM has been applied to the study of
glutamate receptors, revealing their atomic structures, and the conformational changes that underlie their gating. In this review I summarize the history of this field, viewed through the lens of a career in which I spent 3 decades working on the structure and function of
glutamate receptor ion channels.
This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’.