Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons

摘要

Consistent with the epileptogenic and deleterious effects of the potent neurotoxin kainate, the activation of kainate receptors reduces the synaptic inhibition induced by the amino acid γ-ami- nobutyric acid (GABA). Extrapolating from these data led to the conclusion that kainate receptors are located presynaptically. How- ever, kainate directly depolarizes the inhibitory interneurons, caus- ing 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 kainote receptors. Here we show that both effects, membrane depolariza- tion and the reduction of inhibitory potentials, can be dissociated by several means, particularly by the natural agonist of kainate receptors, glutamate. Indeed, when applied at low concentrations. glutamate inhibited GABA release without affecting the firing rate of GABA interneurons. These results indicate that CA1 interneu. rons contain two populations of kainate receptors, each with different agonist sensitivity and coupled to distinct signaling pathways.