Two populations of kainate receptors with separate signaling mechanisms inhippocampal interneurons

Consistent with the epileptogenic and deleterious effects of the potent neu rotoxin kainate, the activation of kainate receptors reduces the synaptic i nhibition induced by the amino acid gamma-aminobutyric acid (GABA). Extrapo lating from these data led to the conclusion that kainate receptors are loc ated presynaptically. However, kainate directly depolarizes the inhibitory interneurons, causing them to fire repeatedly. This effect might indirectly decrease the size of inhibitory postsynaptic currents recorded from pyrami dal cells and places in doubt the presynaptic location for kainate receptor s, Here we show that both effects, membrane depolarization and the reductio n of inhibitory potentials, can be dissociated by several means, particular ly by the natural agonist of kainate receptors, glutamate, Indeed, when app lied at low concentrations, glutamate inhibited GABA release without affect ing the firing rate of GABA interneurons, These results indicate that CA1 i nterneurons contain two populations of kainate receptors, each with differe nt agonist sensitivity and coupled to distinct signaling pathways.