Metabotropic signaling by kainate receptors

Kainate receptors (KARs) are members of the ionotropic glutamate receptor family. Despite their ubiquitous presence in the central nervous system, and in contrast to the better characterized N ‐methyl‐ d ‐aspartates (NMDARs) and α ‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors (AMPARs), the contribution of KARs to synaptic transmission has only been demonstrated in a few central synapses. However, there is now accumulating evidence that KARs are present on both sides of the synapse, where they play distinct and diverse roles. In addition to their contribution to synaptic transmission, KARs can regulate synaptic activity and plasticity either by presynaptically modulating neurotransmitter release at GABAergic and glutamatergic synapses, or by postsynaptically regulating neuronal excitability. This prominent neuromodulatory role of KARs has been further highlighted by the finding that these glutamate‐gated ion‐channels can also signal through G‐proteins and other second messengers. This non‐canonical metabotropic signaling of KARs was firmly established by demonstrating it to be independent of ion flux. The discovery of this dual signaling capacity of KARs constituted a breakthrough in understanding how they function and since then, an increasing number of metabotropic actions of KARs have been reported. It is now clear that this dual signaling underlies the diverse functions of KARs and defining this metabotropic component of the signaling system operated by KARs will be necessary to understand the physiological contributions of glutamate receptors. WIREs Membr Transp Signal 2012, 1:399–410. doi: 10.1002/wmts.35 For further resources related to this article, please visit the WIREs website .