The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons

Eto, Kojiro; Arimura, Yukiko; Nabekura, Junichi; Нода, Мами; Ishibashi, Hiroyuki

doi:10.1016/j.brainres.2007.05.060

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…Brain slices were made as previously reported (Eto et al, 2007). Electrical recordings were made using the conventional whole-cell patch-clamp recording technique at a holding potential of Ϫ60 mV (Axopatch 700B, Molecular Devices).…”

Section: Methodsmentioning

confidence: 99%

Inter-regional Contribution of Enhanced Activity of the Primary Somatosensory Cortex to the Anterior Cingulate Cortex Accelerates Chronic Pain Behavior

et al. 2011

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Multiple cortical areas are involved in pain processing, including the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC). Although accumulations of evidence suggest that the S1 activity increases under chronic pain conditions, whether plastic change occurs or not within the S1, and whether and how the plastic change contributes to chronic pain behavior, is unknown. Here, we provide the first evidence that intra-regional remodeling within the mouse S1 accelerates chronic pain behavior by modulating neuronal activity in the ACC, one of the important cortical areas for chronic pain. Using two-photon Ca 2ϩ imaging, we found that the spontaneous activity of layer 2/3 neurons in the S1 and then response to sensory and layer 4 stimulations increased under chronic pain conditions. In addition, pharmacological attenuation and facilitation of S1 activity attenuated and facilitated the chronic pain behavior, respectively. Furthermore, electrical response of the ACC to peripheral stimulation successfully correlated with S1 neuronal activity, and inhibition of ACC activity alleviated the mechanical allodynia. The present results will provide development of efficient therapeutic strategies against chronic pain by focusing on the S1 and ACC.

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Section: Methodsmentioning

confidence: 99%

Inter-regional Contribution of Enhanced Activity of the Primary Somatosensory Cortex to the Anterior Cingulate Cortex Accelerates Chronic Pain Behavior

et al. 2011

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“…The inhibition of the glycine-evoked current is associated with reduced channel opening (gating) and a decrease in agonist efficacy (Miller et al, 2005a;Eto et al, 2007). Interestingly, in recent years it has been shown that modulation by Zn 21 is related to the effects of ethanol on GlyR, where Zn 21 increases the potentiation of glycinergic currents in presence of ethanol, which occurs in brain regions associated with the development of alcohol addiction (McCracken et al, 2010b(McCracken et al, , 2013Morud et al, 2015).…”

Section: Molecular Sites For the Functional Regulation Of Glyrmentioning

confidence: 99%

Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors

2016

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Glycine receptors (GlyR) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyR are found in the spinal cord and brain stem, and more recently they were reported in higher regions of the CNS such as the hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, and sensory processing, and they are targets for relevant physiologic and pharmacologic modulators. Several studies with protein crystallography and cryoelectron microscopy have shed light on the residues and mechanisms associated with the activation, blockade, and regulation of pentameric Cys-loop ion channels at the atomic level. Initial studies conducted on the extracellular domain of acetylcholine receptors, ion channels from prokaryote homologs-Erwinia chrysanthemi ligand-gated ion channel (ELIC), Gloeobacter violaceus ligand-gated ion channel (GLIC)-and crystallized eukaryotic receptors made it possible to define the overall structure and topology of the Cys-loop receptors. For example, the determination of pentameric GlyR structures bound to glycine and strychnine have contributed to visualizing the structural changes implicated in the transition between the open and closed states of the Cys-loop receptors. In this review, we summarize how the new information obtained in functional, mutagenesis, and structural studies have contributed to a better understanding of the function and regulation of GlyR.

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“…Zn 2+ has a biphasic concentration-dependent effect on GlyRs, producing a potentiation of glycinergic currents at low micromolar concentrations, by mainly increasing channel opening probability and burst duration [59,61]. On the other hand, concentrations higher than 10 μM can inhibit the glycine activated current by decreasing its efficacy and consequently modifying the inhibitory capacity of these receptors [62,63]. The binding sites for Zn 2+ associated with potentiation of channel activity are found on the outer face of the amino-terminal domain of α1 GlyR subunits whereas residues involved in the inhibitory effects are on the opposite side of the same domain [64].…”

Section: Modulatorsmentioning

confidence: 99%

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

Burgos

Muñoz

Guzmán

et al. 2015

Pharmacological Research

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It is well accepted that ethanol is able to produce major health and economic problems associated to its abuse. Because of its intoxicating and addictive properties, it is necessary to analyze its effect in the central nervous system. However, we are only now learning about the mechanisms controlling the modification of important membrane proteins such as ligand-activated ion channels by ethanol. Furthermore, only recently are these effects being correlated to behavioral changes. Current studies show that the glycine receptor (GlyR) is a susceptible target for low concentrations of ethanol (5 to 100 mM). GlyRs are relevant for the effects of ethanol because they are found in the spinal cord and brain stem where they primarily express the α1 subunit. More recently, the presence of GlyRs was described in higher regions, such as the hippocampus and nucleus accumbens, with a prevalence of α2/α3 subunits. Here, we review data on the following aspects of ethanol effects on GlyRs: 1) direct interaction of ethanol with amino acids in the extracellular or transmembrane domains, and indirect mechanisms through the activation of signal transduction pathways; 2) analysis of α2 and α3 subunits having different sensitivities to ethanol which allows the identification of structural requirements for ethanol modulation present in the intracellular domain and C-terminal region; 3) Genetically modified knock-in mice for α1 GlyRs that have an impaired interaction with G protein and demonstrate reduced ethanol sensitivity without changes in glycinergic transmission; and 4) GlyRs as potential therapeutic targets.

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The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons

Cited by 9 publications

References 44 publications

Inter-regional Contribution of Enhanced Activity of the Primary Somatosensory Cortex to the Anterior Cingulate Cortex Accelerates Chronic Pain Behavior

Inter-regional Contribution of Enhanced Activity of the Primary Somatosensory Cortex to the Anterior Cingulate Cortex Accelerates Chronic Pain Behavior

Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

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