Zingerone enhances glutamatergic spontaneous excitatory transmission by activating TRPA1 but not TRPV1 channels in the adult rat substantia gelatinosa

2013 ◽  
Vol 110 (3) ◽  
pp. 658-671 ◽  
Author(s):  
Hai-Yuan Yue ◽  
Chang-Yu Jiang ◽  
Tsugumi Fujita ◽  
Eiichi Kumamoto
Keyword(s):  
Nervous System ◽  
Trp Channels ◽  
Allyl Isothiocyanate ◽  
Substantia Gelatinosa ◽  
Facilitatory Effect ◽  
Afferent Neuron ◽  
Patch Clamp Technique ◽  
Adult Rat ◽  
Excitatory Transmission ◽  
Trpv1 Channels

Transient receptor potential (TRP) channels are thought to play a role in regulating nociceptive transmission to spinal substantia gelatinosa (SG) neurons. It remains to be unveiled whether the TRP channels in the central nervous system are different in property from those involved in receiving nociceptive stimuli in the peripheral nervous system. We examined the effect of the vanilloid compound zingerone, which activates TRPV1 channels in the cell body of a primary afferent neuron, on glutamatergic excitatory transmission in the SG neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. Bath-applied zingerone reversibly and concentration-dependently increased spontaneous excitatory postsynaptic current (EPSC) frequency. This effect was accompanied by an inward current at −70 mV that was resistant to glutamate receptor antagonists. These zingerone effects were repeated and persisted in Na+-channel blocker tetrodotoxin-, La3+-, or IP3-induced Ca2+-release inhibitor 2-aminoethoxydiphenyl borate-containing or Ca2+-free Krebs solution. Zingerone activity was resistant to the selective TRPV1 antagonist capsazepine but sensitive to the nonselective TRP antagonist ruthenium red, the TRPA1 antagonist HC-030031, and the Ca2+-induced Ca2+-release inhibitor dantrolene. TRPA1 agonist allyl isothiocyanate but not capsaicin inhibited the facilitatory effect of zingerone. On the other hand, zingerone reduced monosynaptically evoked EPSC amplitudes, as did TRPA1 agonists. Like allyl isothiocyanate, zingerone enhanced GABAergic spontaneous inhibitory transmission in a manner sensitive to tetrodotoxin. We conclude that zingerone presynaptically facilitates spontaneous excitatory transmission, probably through Ca2+-induced Ca2+-release mechanisms, and produces a membrane depolarization in SG neurons by activating TRPA1 but not TRPV1 channels.

Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons

2009 ◽  
Vol 102 (1) ◽  
pp. 312-319 ◽  
Author(s):  
T. Fujita ◽  
T. Liu ◽  
T. Nakatsuka ◽  
E. Kumamoto
Keyword(s):  
Sensory Processing ◽  
Substantia Gelatinosa ◽  
Activation Mechanism ◽  
Patch Clamp Technique ◽  
Nociceptive Transmission ◽  
Adult Rat ◽  
Excitatory Transmission ◽  
Whole Cell Patch Clamp ◽  
Proteinase Activated Receptors ◽  
Adult Rat Spinal Cord

Proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. A potential impact of PAR on sensory processing has not been fully examined yet. Here we report that synthetic peptides with sequences corresponding to PAR ligands enhance glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. The frequency of spontaneous excitatory postsynaptic current (EPSC) was increased by PAR-1 agonist SFLLRN-NH2 (by 47% at 1 μM) with small increases by PAR-2 and -4 agonists (SLIGKV-NH2 and GYPGQV-OH, respectively; at >3 μM); there was no change in its amplitude or in holding current at −70 mV. The PAR-1 peptide action was inhibited by PAR-1 antagonist YFLLRNP-OH. TFLLR-NH2, an agonist which is more selective to PAR-1 than SFLLRN-NH2, dose-dependently increased spontaneous EPSC frequency (EC50 = 0.32 μM). A similar presynaptic effect was produced by PAR-1 activating proteinase thrombin in a manner sensitive to YFLLRNP-OH. The PAR-1 peptide action was resistant to tetrodotoxin and inhibited in Ca2+-free solution. Primary-afferent monosynaptically evoked EPSC amplitudes were unaffected by PAR-1 agonist. These results indicate that PAR-1 activation increases the spontaneous release of l-glutamate onto SG neurons from nerve terminals in a manner dependent on extracellular Ca2+. Considering that sensory processing within the SG plays a pivotal role in regulating nociceptive transmission to the spinal dorsal horn, the PAR-1-mediated glutamatergic transmission enhancement could be involved in a positive modulation of nociceptive transmission.

Action of thymol on spontaneous excitatory transmission in adult rat spinal substantia gelatinosa neurons

2015 ◽  
Vol 606 ◽  
pp. 94-99 ◽  
Author(s):  
Zhi-Hao Xu ◽  
Chong Wang ◽  
Tsugumi Fujita ◽  
Chang-Yu Jiang ◽  
Eiichi Kumamoto
Keyword(s):  
Substantia Gelatinosa ◽  
Adult Rat ◽  
Excitatory Transmission

Phospholipase A2 Activation Enhances Inhibitory Synaptic Transmission in Rat Substantia Gelatinosa Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1274-1284 ◽  
Author(s):  
Tao Liu ◽  
Tsugumi Fujita ◽  
Terumasa Nakatsuka ◽  
Eiichi Kumamoto
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Glutamate Receptor ◽  
Receptor Activation ◽  
Substantia Gelatinosa ◽  
Facilitatory Effect ◽  
Maximal Effect ◽  
Patch Clamp Technique ◽  
Activity Increase ◽  
Inhibitory Transmission

Phospholipase A2 (PLA2) activation enhances glutamatergic excitatory synaptic transmission in substantia gelatinosa (SG) neurons, which play a pivotal role in regulating nociceptive transmission in the spinal cord. By using melittin as a tool to activate PLA2, we examined the effect of PLA2 activation on spontaneous inhibitory postsynaptic currents (sIPSCs) recorded at 0 mV in SG neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique. Melittin enhanced the frequency and amplitude of GABAergic and glycinergic sIPSCs. The enhancement of GABAergic but not glycinergic transmission was largely depressed by Na+ channel blocker tetrodotoxin or glutamate-receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione and/or dl-2-amino-5-phosphonovaleric acid) and also in a Ca2+-free Krebs solution. The effects of melittin on glycinergic sIPSC frequency and amplitude were dose-dependent with an effective concentration of ∼0.7 μM for half-maximal effect and were depressed by PLA2 inhibitor 4-bromophenacyl bromide or aristolochic acid. The melittin-induced enhancement of glycinergic transmission was depressed by lipoxygenase inhibitor nordihydroguaiaretic acid but not cyclooxygenase inhibitor indomethacin. These results indicate that the activation of PLA2 in the SG enhances GABAergic and glycinergic inhibitory transmission in SG neurons. The former action is mediated by glutamate-receptor activation and neuronal activity increase, possibly the facilitatory effect of PLA2 activation on excitatory transmission, whereas the latter action is due to PLA2 and subsequent lipoxygenase activation and is independent of extracellular Ca2+. It is suggested that PLA2 activation in the SG could enhance not only excitatory but also inhibitory transmission, resulting in the modulation of nociception.

scholarly journals Inhibition byO-desmethyltramadol of glutamatergic excitatory transmission in adult rat spinal substantia gelatinosa neurons

2019 ◽  
Vol 15 ◽  
pp. 174480691882424 ◽  
Author(s):  
Akiko Koga ◽  
Tsugumi Fujita ◽  
Lian-Hua Piao ◽  
Terumasa Nakatsuka ◽  
Eiichi Kumamoto
Keyword(s):  
Substantia Gelatinosa ◽  
Adult Rat ◽  
Excitatory Transmission

Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons

Neuroreport ◽  
2016 ◽  
Vol 27 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Lan Zhu ◽  
Tsugumi Fujita ◽  
Chang-Yu Jiang ◽  
Eiichi Kumamoto
Keyword(s):  
Substantia Gelatinosa ◽  
Adult Rat ◽  
Excitatory Transmission

scholarly journals TRP Channels Involved in Spontaneous L-Glutamate Release Enhancement in the Adult Rat Spinal Substantia Gelatinosa

Cells ◽  
2014 ◽  
Vol 3 (2) ◽  
pp. 331-362 ◽  
Author(s):  
Eiichi Kumamoto ◽  
Tsugumi Fujita ◽  
Chang-Yu Jiang
Keyword(s):  
Trp Channels ◽  
Glutamate Release ◽  
Substantia Gelatinosa ◽  
Adult Rat

Biphasic modulation by galanin of excitatory synaptic transmission in substantia gelatinosa neurons of adult rat spinal cord slices

2011 ◽  
Vol 105 (5) ◽  
pp. 2337-2349 ◽  
Author(s):  
Hai-Yuan Yue ◽  
Tsugumi Fujita ◽  
Eiichi Kumamoto
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Outward Current ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Patch Clamp Technique ◽  
Similar Action ◽  
Membrane Hyperpolarization ◽  
Adult Rat ◽  
Adult Rat Spinal Cord

Although intrathecally administrated galanin modulates nociceptive transmission in a biphasic manner, this has not been fully examined previously. In the present study, the action of galanin on synaptic transmission in the substantia gelatinosa (SG) neurons of adult rat spinal cord slices was examined, using the whole cell patch-clamp technique. Galanin concentration-dependently increased the frequency of spontaneous excitatory postsynaptic current (EPSC; EC50 = 2.0 nM) without changing the amplitude, indicating a presynaptic effect. This effect was reduced in a Ca2+-free, or voltage-gated Ca2+ channel blocker La3+-containing Krebs solution and was produced by a galanin type-2/3 receptor (GalR2/R3) agonist, galanin 2–11, but not by a galanin type-1 receptor (GalR1) agonist, M617. Galanin also concentration-dependently produced an outward current at −70 mV (EC50 = 44 nM), although this appeared to be contaminated by a small inward current. This outward current was mimicked by M617, but not by galanin 2–11. Moreover, galanin reduced monosynaptic Aδ-fiber- and C-fiber-evoked EPSC amplitude; the former reduction was larger than the latter. A similar action was produced by galanin 2–11, but not by M617. Spontaneous and focally evoked inhibitory (GABAergic and glycinergic) transmission was unaffected by galanin. These findings indicate that galanin at lower concentrations enhances the spontaneous release of l-glutamate from nerve terminals by Ca2+ entry from the external solution following GalR2/R3 activation, whereas galanin at higher concentrations also produces a membrane hyperpolarization by activating GalR1. Moreover, galanin reduces l-glutamate release onto SG neurons from primary afferent fibers by activating GalR2/R3. These effects could partially contribute to the behavioral effect of galanin.

Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1)

2000 ◽  
Vol 92 (2) ◽  
pp. 473-473 ◽  
Author(s):  
Hiroshi Baba ◽  
Koki Shimoji ◽  
Megumu Yoshimura
Keyword(s):  
Spinal Cord ◽  
Substantia Gelatinosa ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Nociceptive Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Adult Rat ◽  
Postsynaptic Currents

Background The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.

scholarly journals Cellular Mechanisms for Antinociception Produced by Oxytocin and Orexins in the Rat Spinal Lamina II—Comparison with Those of Other Endogenous Pain Modulators

2019 ◽  
Vol 12 (3) ◽  
pp. 136 ◽  
Author(s):  
Eiichi Kumamoto
Keyword(s):  
Membrane Depolarization ◽  
Cellular Mechanisms ◽  
Patch Clamp Technique ◽  
Inhibitory Transmission ◽  
Nociceptive Transmission ◽  
Adult Rat ◽  
Excitatory Transmission ◽  
Transmission Enhancement ◽  
Antinociceptive Mechanisms ◽  
Spinal Lamina

Much evidence indicates that hypothalamus-derived neuropeptides, oxytocin, orexins A and B, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to unveil cellular mechanisms for this antinociception, the effects of the neuropeptides on synaptic transmission were examined in spinal lamina II neurons that play a crucial role in antinociception produced by various analgesics by using the whole-cell patch-clamp technique and adult rat spinal cord slices. Oxytocin had no effect on glutamatergic excitatory transmission while producing a membrane depolarization, γ-aminobutyric acid (GABA)-ergic and glycinergic spontaneous inhibitory transmission enhancement. On the other hand, orexins A and B produced a membrane depolarization and/or a presynaptic spontaneous excitatory transmission enhancement. Like oxytocin, orexin A enhanced both GABAergic and glycinergic transmission, whereas orexin B facilitated glycinergic but not GABAergic transmission. These inhibitory transmission enhancements were due to action potential production. Oxytocin, orexins A and B activities were mediated by oxytocin, orexin-1 and orexin-2 receptors, respectively. This review article will mention cellular mechanisms for antinociception produced by oxytocin, orexins A and B, and discuss similarity and difference in antinociceptive mechanisms among the hypothalamic neuropeptides and other endogenous pain modulators (opioids, nociceptin, adenosine, adenosine 5’-triphosphate (ATP), noradrenaline, serotonin, dopamine, somatostatin, cannabinoids, galanin, substance P, bradykinin, neuropeptide Y and acetylcholine) exhibiting a change in membrane potential, excitatory or inhibitory transmission in the spinal lamina II neurons.

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