Modulation of the glycine response by Ca2+-permeable AMPA receptors in ratspinal neurones

1. In acutely isolated rat sacral dorsal commisural nucleus (SDCN) neurones , application of kainate (KA) reversibly potentiated glycine-evoked Cl- cur rents (I-Gly) in a concentration-dependent manner. 2. The cellular events underlying the interaction between non-NMDA receptor s 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 potentia l for I-Gly. In dose-response curves, KA potentiated lo, without significan tly changing glycine binding affinity. 4. GYKI 52466 blocked while NS-102 had no effect on the KB-induced potentia tion of I-Gly. 5. The potentiation was reduced when KA was applied in a Ca2+-free extracel lular solution or in the presence of BAPTA AM, and was independent of the a ctivation of voltage-dependent Ca2+ channels. 6. Pretreatment with KN-62, a selective Ca2+-calmodulin-dependent protein k inase II (CaMKII) inhibitor, abolished the action of KA. Inhibition of calc ineurin converted the KA-induced potentiation to a sustained one. 7. Single-channel recordings revealed that KA decreased the mean closing ti me of glycine-gated single-channel activity, resulting in an increase in th e probability of channel opening. 8. It is proposed that Ca2+ entry through AMPA receptors modulates the glyc ine receptor function via coactivation of CaMKII and calcineurin in SDCN ne urones. This interaction may provide a ne iv postsynaptic mechanism for con trol of inhibitory synaptic signalling and represent one of the important r egulatory mechanisms of spinal nociception.