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

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.

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

“…This result suggested that the increases of glycine in the interstitium by theanine might have influenced dopamine release via glycine receptors. Although glycine is known as a major inhibitory neurotransmitter, glycine combines with the glycine binding site of the NMDA receptor and enhances excitatory neurotransmission (Xu et al 1999;Kuhse et al 1995;Nong et al 2003). Glycine enhanced NMDA evoked dopamine release, and 7-chloro-kynurenate, an NMDA antagonist, acting on a glycine site, markedly reduced this response (Martinez et al 1992); however, 5,7-DCKA injection did not prevent the increase of dopamine concentration by theanine injection in this study.…”

“…From these data, we expected that not only glycine but also other factors were involved in the effect of theanine on dopamine concentration in the perfusate. It was shown that glycine is co-localized with GABA in astrocytes and interneurons (Ross and Soltesz 2001;Bureau and Mulle 1998;Xu et al 1999;Levi and Patrizio 1992), and glycine and GABA are released simultaneously and work synergistically on different targets (Bohlhalter et al 1994). We expected that the GABAergic nervous system may also be influenced by theanine injection and is involved in dopamine concentration increase in the perfusate; however we did not examined the effect of theanine on intersutitial GABA concentration and GABA receptors in this study.…”

“…It was reported that inhibitory neurotransmitters, such as glycine and GABA, are released by activating a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, ionotropic glutamate receptors (Ross and Soltesz 2001; Bureau and Mulle 1998;Xu et al 1999), and recent reports showed that activating AMPA/kainate receptors facilitated electrically evoked dopamine efflux in guinea pig striatal slices, and glycine and GABA release from astrocytes and interneurons (Antonelli et al 1997;Han et al 2000). In addition, it was shown that theanine bound to AMPA receptors not to NMDA receptors (Kakuda et al 2002a).…”

Ethanol Suppresses Fast Potentiation of Glycine Currents by Glutamate

“…Bearing in mind that ethanol alters intracellular Ca 2ϩ (for review, see Little, 1991;Simasko et al, 1999;Mennerick and Zorumski, 2000), interactions between ethanol and glycine receptors may involve mechanisms linked to intracellular Ca 2ϩ . Three recent studies have reported that glutamateinduced Ca 2ϩ entry greatly potentiates I Gly in spinal neurons or oocytes expressing glycine receptors (Xu et al, 1999(Xu et al, , 2000Fucile et al, 2000). However, the effects of glutamate on VTA glycine receptors have not been examined.…”

Insulin-Like Growth Factor-1 Inhibits Adult Supraoptic Neurons via Complementary Modulation of Mechanoreceptors and Glycine Receptors

“…Tyrosine phosphorylation of the ␤ subunit of GlyR has been shown to potentiate GlyR by a twofold increase in apparent agonist affinity (Caraiscos et al, 2002), an effect remarkably similar to that induced by IGF-1 on SON neuron GlyR. Other kinases (PKC, calcium calmodulin-dependent protein kinase II) are known to also potentiate GlyR but not through a change in agonist sensitivity (Xu et al, 1996(Xu et al, , 1999. Increased agonist affinity also implies enhanced desensitization, which could potentially result in a decreased effect of GlyR activation.…”