ABSTRACT
Ionotropic glutamate receptors underlie fast excitatory transmission at many central synapses. The fusion of a presynaptic vesicle with the nerve-terminal membrane allows the release of a packet of glutamate into the narrow synaptic cleft. This short-lived chemical signal is converted into an electrical event when neurotransmitter molecules bind to receptors, opening ion channels in the postsynaptic membrane. There is little doubt that many of the principles of transmission, established at the neuromuscular junction (Katz, 1969), also apply at excitatory central synapses. However, important differences do occur. One of the most striking is the variety of functionally distinct postsynaptic receptors that are found in central neurons (reviewed by McBain and Mayer, 1994; Hollmann and Heinemann, 1994; Whiting and Priestley, 1998; Dingledine et al., 1999). The subunits that form glutamate receptors are differentially expressed in the CNS, and their distribution changes during development. Thus individual neuron types express distinct complements of the subunits (Monyer et al., 1994; Akazawa et al., 1995; Geiger et al., 1995; Hollmann and Heinemann, 1994). The resulting heterogeneity in receptor properties allows glutamate to give rise to diverse responses. Information about the mechanisms underlying this diversity in signalling has come from a powerful combination of molecular, functional and pharmacological techniques. This chapter is intended to provide an introductory description of the physiology and pharmacology of glutamate receptors, highlighting some of the key properties of these receptors in relation to their constituent subunits. The following topics will be considered: (1) main classes of receptors, subunits and assemblies; (2) pharmacological properties of AMPA-and kainate-Rs; (3) functional diversity of non-NMDARs; (4) pharmacological and functional characteristics of NMDARs; (5) NMDAR diversity in the CNS.
