Most of our knowledge of the synaptic function of kainate receptors stems from a detailed analysis of synaptic transmission between dentate granule cells and CA3 pyramidal neurons, where kainate receptors mediate a slow excitatory current with integrative properties ideally suited for repetitive neuronal firing. Besides this well characterized ionotropic effect of kainate receptors, they can also enhance neuronal excitability by inhibiting the slow Ca(2+) activated K(+) current I(sAHP) via a G-protein coupled mechanism. This phenomenon is associated with Ca(2+) mobilization and protein-kinase activation and ultimately leads to modulation of ion channels responsible for intrinsic electrical properties such as firing adaptation. The significance for CNS function of these newly emerging metabotropic kainate receptors is poorly understood and as yet proteomic analysis of kainate receptors has yielded little information on signaling molecules associated with the kainate receptor ionophore. This chapter covers the key findings that have led to the proposal that high-affinity postsynaptic kainate receptors trigger a form of metabotropic signaling regulating I(sAH P) and neuronal firing in CA3 hippocampal neurons.