Kainate receptors and synaptic transmission
Introduction
Kainate receptors are one of three subtypes of ionotropic receptors for the excitatory transmitter l-glutamate (Dingledine et al., 1999). The other two subtypes, which are named for the synthetic agonists N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), are known to mediate postsynaptic currents at excitatory synapses throughout the brain and spinal cord (Mayer and Westbrook, 1987). The physiological properties of kainate receptors (Chittajallu et al., 1999, Lerma et al., 2001), and their roles in synaptic transmission (Frerking and Nicoll, 2000, Kullmann, 2001, Lerma, 2003), have been discerned only recently, following the discovery of selective antagonists that allow for isolation of kainate receptor-mediated currents (Paternain et al., 1995, Wilding and Huettner, 1995, Bleakman et al., 1996a). Additional interest in kainate receptors has been raised by the cloning and characterization of their subunit cDNAs (Hollmann and Heinemann, 1994), and by the recognition that kainate receptor subunits are distinct from subunits that contribute to AMPA receptors (Boulter et al., 1990, Keinanen et al., 1990) and to NMDA receptors (Kutsuwada et al., 1992, Monyer et al., 1992, Moriyoshi et al., 1991).
Section snippets
Kainate receptor properties
Kainate receptors were originally defined by Watkins and coworkers (Davies et al., 1979, Watkins and Evans, 1981) based on the pharmacology of neuronal responses to excitatory amino acids. In particular, the selective depolarization of isolated dorsal root fibers by kainate led them to propose a unique receptor for kainate that was distinct from the binding sites activated by NMDA and AMPA.
Hippocampus
Detailed study of the role of kainate receptors in synaptic transmission has only been possible since the discovery of selective AMPA receptor antagonists in 1995 (Paternain et al., 1995, Wilding and Huettner, 1995, Bleakman et al., 1996a). Before that time, a number of reports described interesting effects on excitability (Robinson and Deadwyler, 1981, Westbrook and Lothman, 1983) and synaptic transmission (Collingridge et al., 1983, Kehl et al., 1984, Fisher and Alger, 1984) following
Perspectives
In many regions of the nervous system, the involvement of presynaptic and/or postsynaptic kainate receptors in synaptic transmission is now firmly established. Although controversies and uncertainties remain, a number of general themes have emerged. First, activation of kainate receptors produces bi-directional modulation of both excitatory and inhibitory transmission. Low to moderate activation enhances transmission, whereas stronger activation inhibits transmission. Second, synaptic currents
Acknowledgements
I am grateful to the NIH for supporting my research (NS30888) and to Geoff Swanson, Tim Wilding and Geoff Kerchner for careful reading of the manuscript.
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