Modulation of the glycine response by Ca2+‐permeable AMPA receptors in rat spinal neurones

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Abstract
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. 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. 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. GYKI 52466 blocked while NS-102 had no effect on the KA-induced potentiation of IGly. 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. 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. 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. 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.