Glutamate receptors of the kainate type (Kainate receptors, KARs), are mediators of ionotropic postsynaptic synaptic transmission, as well as presynaptic modulators of neurotransmitter release where they show both ionotropic and metabotropic actions regulating glutamate and γ-aminobutiric acid (GABA) release. The mechanisms underlying these modulatory roles are starting to be understood at some brain regions. Here we review the KARs roles and mechanisms involved in the modulation of glutamate release in the cerebellum at parallel fibers (PF)-Purkinje Cells (PuC) synapses. KARs activation mediate a biphasic effect on glutamate release at this synapse, with low kainate (KA) concentrations mediating a facilitation of glutamate release and higher KA concentrations mediating a depression of glutamate release. KA-mediated facilitation is prevented by antagonizing KARs, by inhibition of PKA or stimulation of adenylyl cyclase (AC), by blocking Ca2+ permeant KARs, by depleting intracellular Ca2+ stores and by blocking calmodulin. Thus, at cerebellar parallel fiber-Purkinje cell synapses, presynaptic KARs mediate glutamate release facilitation through Ca2+-calmodulin dependent activation of adenylyl cyclase/cAMP/protein kinase A signaling. KAR-mediated depression of glutamate release involves the AC/cAMP/PKA pathway as for facilitation but not Ca2+-calmodulin, being in this case AC activated by a Gi/o protein to mediate a depression of glutamate release.
Part of the book: Biogenic Amines in Neurotransmission and Human Disease