Effect of protein kinase C activation on the glycine evoked Cl− current in spinal cord neurons

Albarran, Felipe A.; Roa, Jorge; Olivares-Navarrete, René; Castillo, Reinaldo Vargas; Nualart, Francisco; Aguayo, Luis G.

doi:10.1016/s0006-8993(01)02255-7

Cited by 19 publications

(12 citation statements)

References 28 publications

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“…PKA increases the channel opening probability in trigeminal neurons (4,23), but inhibits glycine responses in hypothalamic neurons (6). Similarly, PKC has been shown to inhibit glycine currents in hippocampal, trigeminal, and spinal neurons (8,23,24). In the salamander retinal ganglion cells, PKA down-regulated the glycine current slow component, while PKC up-regulated the glycine current fast component (25).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Strychnine-sensitive Glycine Receptor in the Intact Frog Retina: Modulation by Protein Kinases

Salceda

Aguirre-Ramírez

2005

Neurochem Res

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We studied 3H-glycine and 3H-strychnine specific binding to glycine receptor (GlyR) in intact isolated frog retinas. To avoid glycine binding to glycine uptake sites, experiments were performed at low ligand concentrations in a sodium-free medium. The binding of both radiolabeled ligands was saturated. Scatchard analysis of bound glycine and strychnine revealed a KD of 2.5 and 2.0 microM, respectively. Specific binding of glycine was displaced by beta-alanine, sarcosine, and strychnine. Strychnine binding was displaced 50% by glycine, and sarcosine. Properties of the strychnine-binding site in the GlyR were modified by sarcosine. Binding of both radioligands was considerably reduced by compounds that inhibit or activate adenylate cyclase and increased cAMP levels. A phorbol ester activator of PKC remarkably decreased glycine and strychnine binding. These results suggest modulation of GlyR in response to endogenous activation of protein kinases A and C, as well as protein phosphorylation modulating GlyR function in retina.

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Section: Discussionmentioning

confidence: 99%

Characterization of Strychnine-sensitive Glycine Receptor in the Intact Frog Retina: Modulation by Protein Kinases

Salceda

Aguirre-Ramírez

2005

Neurochem Res

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“…However, until now, the consequences of these modifications are extensively debated due to discrepancies in the response of the GlyR. PKC activation using phorbol myristate acetate (PMA) results in a decrease in chloride currents evoked by glycine in the spinal cord [76,77] and recombinant receptors expressed in Xenopus laevis [78]. Conversely, in hippocampal and dissociated sacral dorsal commissural neurons, an increase in glycinergic currents were found upon PKC activation, either through the use of PMA or indirectly by stimulation of serotonin receptor type 2 affecting in both cases serine 391 and 398 in α1 and β subunits, respectively [79,80].…”

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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“…GlyR LTP may require Ca 2+ -mediated glycine receptor delivery to synapses, as chelating postsynaptic Ca 2+ was sufficient to impair LTP induction. Alternatively, IL-1β may increase channel open probability rather than number; glycinergic currents and single-channel openings are transiently increased by Ca 2+ (11), or by a number of neuromodulators downstream of intracellular Ca 2+ , including PKC, calcium/calmodulin-dependent protein kinase II, and endocannabinoids (11,(54)(55)(56)(57)(58)(59)(60)(61)(62). Similar signaling processes may mediate LTP described at goldfish Mauthner cell glycinergic synapses, where underlying mechanisms have not been investigated (63).…”

Section: Glycine Receptor Trafficking and Channel Properties Modulatementioning

confidence: 99%

Long-term potentiation of glycinergic synapses triggered by interleukin 1β

Chirila

Brown

Bishop

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Long-term potentiation (LTP) is a persistent increase in synaptic strength required for many behavioral adaptations, including learning and memory, visual and somatosensory system functional development, and drug addiction. Recent work has suggested a role for LTP-like phenomena in the processing of nociceptive information in the dorsal horn and in the generation of central sensitization during chronic pain states. Whereas LTP of glutamatergic and GABAergic synapses has been characterized throughout the central nervous system, to our knowledge there have been no reports of LTP at mammalian glycinergic synapses. Glycine receptors (GlyRs) are structurally related to GABA A receptors and have a similar inhibitory role. Here we report that in the superficial dorsal horn of the spinal cord, glycinergic synapses on inhibitory GABAergic neurons exhibit LTP, occurring rapidly after exposure to the inflammatory cytokine interleukin-1 beta. This form of LTP (GlyR LTP) results from an increase in the number and/or change in biophysical properties of postsynaptic glycine receptors. Notably, formalin-induced peripheral inflammation in vivo potentiates glycinergic synapses on dorsal horn neurons, suggesting that GlyR LTP is triggered during inflammatory peripheral injury. Our results define a previously unidentified mechanism that could disinhibit neurons transmitting nociceptive information and may represent a useful therapeutic target for the treatment of pain.G lycine mediates fast synaptic inhibition throughout the spinal cord, brainstem, and midbrain, controlling normal motor behavior and rhythm generation, somatosensory processing, auditory and retinal signaling, and coordination of reflex responses (1). Strychnine-sensitive glycine receptors (GlyRs) are pentameric ligand-gated chloride channels of the Cys-loop receptor family that together with GABA A receptors (GABA A Rs) dynamically interact with the synaptic scaffold protein gephyrin to form inhibitory synapses (1, 2). In the dorsal horn of the spinal cord, glycinergic synapses are essential for nociceptive and tactile sensory processing both during adaptive and pathological pain states (3-7). However, compared with glutamatergic and GABAergic synapses, little is known about the regulation of their synaptic strength. Several studies have examined glycine receptor trafficking in cultured neurons and in heterologous expression systems (8, 9). Intracellular Ca 2+ appears important in the stabilization of GlyRs at synapses in culture (10), and elevation of intracellular Ca 2+ can also potently increase glycine receptor single channel openings in cultured cells and in heterologous systems (11). However, the modulation of glycinergic synaptic strength in native tissue remains relatively unexplored.Following peripheral injury or inflammation, changes in tactile perception develop, including hyperalgesia (exaggerated pain upon noxious stimulation), allodynia (pain in response to innocuous stimuli), and secondary hyperalgesia (pain spreading beyond the confines of the injure...

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Effect of protein kinase C activation on the glycine evoked Cl− current in spinal cord neurons

Cited by 19 publications

References 28 publications

Characterization of Strychnine-sensitive Glycine Receptor in the Intact Frog Retina: Modulation by Protein Kinases

Characterization of Strychnine-sensitive Glycine Receptor in the Intact Frog Retina: Modulation by Protein Kinases

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

Long-term potentiation of glycinergic synapses triggered by interleukin 1β

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