Direct presynaptic regulation of GABA/glycine release by kainate receptorsin the dorsal horn: An ionotropic mechanism

In the spinal cord dorsal horn, excitatory sensory fibers terminate adjacen t to interneuron terminals. Here, we show that kainate (KA) receptor activa tion triggered action potential-independent release of GABA and glycine fro m dorsal horn interneurons. This release was transient, because KA receptor s desensitized, and it required Na+ entry and Ca2+ channel activation. KA m odulated evoked inhibitory transmission in a dose-dependent, biphasic manne r, with suppression being more prominent. In recordings from isolated neuro n pairs, this suppression required GABA(B) receptor activation, suggesting that KA-triggered GABA release activated presynaptic GABA(B) autoreceptors. Finally, glutamate released from sensory fibers caused a KA and GABA(B) re ceptor-dependent suppression of inhibitory transmission in spinal slices. T hus, we show how presynaptic KA receptors are linked to changes in GABA/gly cine release and highlight a novel role for these receptors in regulating s ensory transmission.