Kainate receptor inhibitory presynaptic receptors

Facilitatory actions of presynaptic kainate receptors (82,88) were long overshadowed by the pronounced inhibitory effects of kainate receptor agonists on both gluta-matergic and GABAergic transmission. Recently, facilitation of synaptic transmission via activation of a presynaptic kainate receptors has been described in the GABAergic synapses in area CA1 (86), in the spinal cord (99), and probably most thoroughly, in the mossy-hber synapse in area CA3 (39,77,100). 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and 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. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). 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. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Scanziani M, Capogna M, Gahwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9 919-27 Schlicker E, Gothert M (1998) Interactions between the presynaptic alpha2-autoreceptor and presynaptic inhibitory heteroreceptors on noradrenergic neurones. Brain Res Bull 47 129-32. Schmitz D, Mellor J, Nicoll RA (2001) Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291 1972-6 Schneggenburger R, Neher E (2005) Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol 15 266-74... 

Xu H, Wu L-J, Zhao M-G, Toyoda H, Vadakkan K, Jia Y, Pinaud R, Zhuo M (2006) Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Molec Pain 2 29... 

Unlike other transmitter systems, there are no obvious meehanisms for dampening glutamate release. Presynaptic autoreceptors for glutamate are mostly of the kainate type (see below) and appear to act as positive rather than negative influenees on further release of the amino acid. Although poorly characterised at present, inhibitory autoreceptors of the metabotropic type of receptors may act to inhibit release of glutamate. 

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