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.

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.

Activation of Presynaptic Group III Metabotropic Receptors Enhances Glutamate Release in Rat Entorhinal Cortex

2000 ◽  
Vol 83 (5) ◽  
pp. 2519-2525 ◽  
Author(s):  
D. Ieuan Evans ◽  
Roland S. G. Jones ◽  
Gavin Woodhall
Keyword(s):  
Synaptic Transmission ◽  
Entorhinal Cortex ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Facilitatory Effect ◽  
Metabotropic Receptors ◽  
Patch Clamp Technique ◽  
Group Iii ◽  
Bath Application ◽  
Layer V

The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 μM) resulted in a marked facilitation of both spontaneous and activity-independent “miniature” (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 μM) on sEPSC frequency prevailed in the presence ofdl−2-amino-5-phosphonopentanoic acid (100 μM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 μM). These data confirmed that group III mGluRs, and not N-methyl-d-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (20 μM) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.

scholarly journals Differential Regulation of Two Distinct Voltage-Dependent Sodium Currents by Group III Metabotropic Glutamate Receptor Activation in Insect Pacemaker Neurons

2006 ◽  
Vol 96 (5) ◽  
pp. 2437-2450 ◽  
Author(s):  
Céline Lavialle-Defaix ◽  
Hélène Gautier ◽  
Antoine Defaix ◽  
Bruno Lapied ◽  
Françoise Grolleau
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Activation ◽  
Camp Level ◽  
Neuronal Firing ◽  
Intracellular Camp ◽  
Sodium Currents ◽  
Patch Clamp Technique ◽  
Metabotropic Glutamate ◽  
Voltage Dependent

Using whole cell patch-clamp technique and immunocytochemistry on adult dorsal unpaired median (DUM) neurons isolated from the cockroach Periplaneta americana CNS, we reported the characterization of a native mGluR, sharing pharmacological properties with vertebrate metabotropic glutamate receptor III (mGluRIII) that regulated voltage-dependent sodium current ( INa). The global INa was dissociated by means of l-glutamate sensitivity, deactivation time constant, voltage dependence of activation and inactivation, recovery from inactivation, and intracellular regulation process. These two currents were respectively designated INa1 and INa2 for l-glutamate-sensitive and -insensitive sodium currents. l-glutamate selectively reduced INa1 by an increase of intracellular cAMP level. Using different activators and/or inhibitors of G proteins and cAMP/PKA cascade, together with St-Ht31 (an inhibitor of PKA binding to AKAP) and AKAP-79 antibodies, we established that mGluRIII was linked to INa1 by a Gi/o and a suspected Gs protein. According to the activated signaling pathway, l-glutamate elevated the cAMP level, which thereby activated cytosolic PKA and released PKA bound to AKAP. As expected from both biophysical and pharmacological studies, we showed that, through an inhibition of INa1, l-glutamate increased DUM neuron spontaneous electrical activity. These results indicated that such mGluRIII-activated dual processes provided a new physiological control of pacemaker neuronal firing.

scholarly journals Effect of galanin on excitatory and inhibitory synaptic transmission in substantia gelatinosa neurons of rat spinal cord slices

PAIN RESEARCH ◽  
2010 ◽  
Vol 25 (3) ◽  
pp. 159-169
Author(s):  
Hai-Yuan Yue ◽  
Tsugumi Fujita ◽  
Lian-Hua Piao ◽  
Takahiro Aoyama ◽  
Satoko Uemura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Inhibitory Synaptic Transmission

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.

Synaptic modulation and inward current produced by oxytocin in substantia gelatinosa neurons of adult rat spinal cord slices

2014 ◽  
Vol 111 (5) ◽  
pp. 991-1007 ◽  
Author(s):  
Chang-Yu Jiang ◽  
Tsugumi Fujita ◽  
Eiichi Kumamoto
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Oxytocin Receptor ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Inhibitory Transmission ◽  
Inward Current ◽  
Adult Rat ◽  
Adult Rat Spinal Cord

Cellular mechanisms for antinociception produced by oxytocin in the spinal dorsal horn have not yet been investigated thoroughly. We examined how oxytocin affects synaptic transmission in substantia gelatinosa neurons, which play a pivotal role in regulating nociceptive transmission, by applying the whole-cell patch-clamp technique to the substantia gelatinosa neurons of adult rat spinal cord slices. Bath-applied oxytocin did not affect glutamatergic spontaneous, monosynaptically-evoked primary-afferent Aδ-fiber and C-fiber excitatory transmissions. On the other hand, oxytocin produced an inward current at −70 mV and enhanced GABAergic and glycinergic spontaneous inhibitory transmissions. These activities were repeated with a slow recovery from desensitization, concentration-dependent and mimicked by oxytocin-receptor agonist. The oxytocin current was inhibited by oxytocin-receptor antagonist, intracellular GDPβS, U-73122, 2-aminoethoxydiphenyl borate, but not dantrolene, chelerythrine, dibutyryl cyclic-AMP, CNQX, Ca2+-free and tetrodotoxin, while the spontaneous inhibitory transmission enhancements were depressed by tetrodotoxin. Current-voltage relation for the oxytocin current reversed at negative potentials more than the equilibrium potential for K+, or around 0 mV. The oxytocin current was depressed in high-K+, low-Na+ or Ba2+-containing solution. Vasopressin V1A-receptor antagonist inhibited the oxytocin current, but there was no correlation in amplitude between a vasopressin-receptor agonist [Arg8]vasopressin and oxytocin responses. It is concluded that oxytocin produces a membrane depolarization mediated by oxytocin but not vasopressin-V1A receptors, which increases neuronal activity, resulting in the enhancement of inhibitory transmission, a possible mechanism for antinociception. This depolarization is due to a change in membrane permeabilities to K+ and/or Na+, which is possibly mediated by phospholipase C and inositol 1,4,5-triphosphate-induced Ca2+-release.

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