Modulation of the glycine response by Ca2+-permeable AMPA receptors in rat spinal neurones.
1. In acutely isolated rat sacral dorsal commisural nucleus (SDCN) neurones, application of kainate (KA) reversibly potentiated glycine-evoked Cl- currents (IGly) in a concentration-dependent manner. 2. The cellular events underlying the interaction between non-NMDA receptors and glycine receptors were studied by using nystatin-perforated patch and cell-attached single-channel recording modes. 3. The action of KA was not accompanied by a shift in the reversal potential for IGly. In dose-response curves, KA potentiated IGly without significantly changing glycine binding affinity. 4. GYKI 52466 blocked while NS-102 had no effect on the KA-induced potentiation of IGly. 5. The potentiation was reduced when KA was applied in a Ca2+-free extracellular solution or in the presence of BAPTA AM, and was independent of the activation of voltage-dependent Ca2+ channels. 6. Pretreatment with KN-62, a selective Ca2+-calmodulin-dependent protein kinase II (CaMKII) inhibitor, abolished the action of KA. Inhibition of calcineurin converted the KA-induced potentiation to a sustained one. 7. Single-channel recordings revealed that KA decreased the mean closing time of glycine-gated single-channel activity, resulting in an increase in the probability of channel opening. 8. It is proposed that Ca2+ entry through AMPA receptors modulates the glycine receptor function via coactivation of CaMKII and calcineurin in SDCN neurones. This interaction may provide a new postsynaptic mechanism for control of inhibitory synaptic signalling and represent one of the important regulatory mechanisms of spinal nociception.
Xu
T L
TL
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. xutianle@physiol2.med.kyushu-u.ac.jp
Li
J S
JS
Jin
Y H
YH
Akaike
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism*; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D018009:Receptors, Glycine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007608:Kainic Acid; D002118:Calcium; D005998:Glycine