Kainate receptors and synaptic transmission

Abstract

Excitatory glutamatergic transmission involves a variety of different receptor types, each with distinct properties and functions. Physiological studies have identified both post- and presynaptic roles for kainate receptors, which are a subtype of the ionotropic glutamate receptors. Kainate receptors contribute to excitatory postsynaptic currents in many regions of the central nervous system including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are co-distributed with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors: for example, in the retina at connections made by cones onto off bipolar cells. Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation; however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. Recent analysis of knockout mice lacking one or more of the subunits that contribute to kainate receptors, as well as studies with subunit-selective agonists and antagonists, have revealed the important roles that kainate receptors play in short- and long-term synaptic plasticity. This review briefly addresses the properties of kainate receptors and considers in greater detail the physiological analysis of their contributions to 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).