Direct Presynaptic Regulation of GABA/Glycine Release by Kainate Receptors in the Dorsal Horn: An Ionotropic Mechanism

• Published in: Neuron (Cambridge, Mass.) Mass.), 2001-11, Vol.32 (3), p.477-488
• Main Authors: Kerchner, Geoffrey A, Wang, Guo-Du, Qiu, Chang-Shen, Huettner, James E, Zhuo, Min
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Cells, Cultured; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists - pharmacology; gamma-Aminobutyric Acid - metabolism; Glycine - metabolism; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Kainic Acid - pharmacology; Male; Posterior Horn Cells - drug effects; Posterior Horn Cells - metabolism; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Receptors, Kainic Acid - physiology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(01)00479-2

In the spinal cord dorsal horn, excitatory sensory fibers terminate adjacent to interneuron terminals. Here, we show that kainate (KA) receptor activation triggered action potential-independent release of GABA and glycine from dorsal horn interneurons. This release was transient, because KA receptors desensitized, and it required Na + entry and Ca 2+ channel activation. KA modulated evoked inhibitory transmission in a dose-dependent, biphasic manner, with suppression being more prominent. In recordings from isolated neuron 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 receptor-dependent suppression of inhibitory transmission in spinal slices. Thus, we show how presynaptic KA receptors are linked to changes in GABA/glycine release and highlight a novel role for these receptors in regulating sensory transmission.