Stimulation of transient receptor potential vanilloid 4 channel suppresses abnormal activation of microglia induced by lipopolysaccharide

Konno, Masakazu; Shirakawa, Hisashi; Iida, Shota; Sakimoto, Shinya; Matsutani, Ikkei; Miyake, Takahito; Kageyama, Keiko; Nakagawa, Takayuki; Shibasaki, Kazuo; Kaneko, Shuji

doi:10.1002/glia.22306

Cited by 72 publications

(56 citation statements)

References 39 publications

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“…TRPV4-positive staining was also observed in a subpopulation of primary afferents, as reported previously (29,40,55,56). Consistent with these results, studies on glial cells of the central nervous system have demonstrated that TRPV4 is expressed by a subpopulation of astrocytes and microglia, suggesting that TRPV4 regulates Ca 2ϩ -dependent processes in glia throughout central and peripheral nervous systems (33,57,58).…”

Section: Discussionsupporting

confidence: 89%

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P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

Rajasekhar

Poole

Liedtke

et al. 2015

Journal of Biological Chemistry

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Background:The function of TRP channels in satellite glial cells is unknown. Results: The proinflammatory, mechanosensitive TRPV4 channel is expressed by satellite glial cells. P2Y 1 receptors cause protein kinase C-dependent activation of TRPV4. Conclusion: TRPV4 enhances purinergic signaling in non-neuronal cells of sensory ganglia. Significance: TRPV4-mediated signaling in satellite glial cells may contribute to inflammatory pain.

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Section: Discussionsupporting

confidence: 89%

“…Cultured DRG-The expression and function of TRP ion channels has been reported in neurons and glial cell types of the central and peripheral nervous systems (6,33,34). However, TRP channel activity in SGCs has not been investigated in detail.…”

Section: Maintaining Neuron-sgc Interactions In Dissociated Andmentioning

confidence: 99%

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

Rajasekhar

Poole

Liedtke

et al. 2015

Journal of Biological Chemistry

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“…Moreover, pharmacological blockade of TRPV4 channels abrogated the ability of PAs to sustain flow/pressureevoked PA constrictions. Of caution is the fact that bath application of TRPV4 channel blocker will target TRPV4 channels expressed in other cell types, such as microglia (Konno et al, 2012) and neurons (Lee and Choe, 2014). However, the observations obtained from the BAPTA experiments (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with an important role for TRPV4 channels in vesselto-astrocyte communication, both in vitro and in vivo studies showed a significant decrease in the number of responding astrocytes in the TRPV4 Ϫ/Ϫ mouse. The partial persistence of astrocytic Ca 2ϩ responses in TRPV4 Ϫ/Ϫ mice may be due to the fact that TRPV4 channels can heteromerize with TRPC1 (Ma et al, 2011) or TRPP2 (Köttgen et al, 2008 channels to form functional channels. Alternatively, and, as with NVC mechanisms, multiple other channels/receptors may contribute to this process.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte Contributions to Flow/Pressure-Evoked Parenchymal Arteriole Vasoconstriction

et al. 2015

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Basal and activity-dependent cerebral blood flow changes are coordinated by the action of critical processes, including cerebral autoregulation, endothelial-mediated signaling, and neurovascular coupling. The goal of our study was to determine whether astrocytes contribute to the regulation of parenchymal arteriole (PA) tone in response to hemodynamic stimuli (pressure/flow). Cortical PA vascular responses and astrocytic Ca 2ϩ dynamics were measured using an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca 2ϩ imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca 2ϩ . Astrocytic Ca 2ϩ responses were corroborated in vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca 2ϩ . In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca 2ϩ ) and enhanced when high Ca 2ϩ or ATP were introduced to the astrocytic syncytium. Bath application of either the TRPV4 channel blocker HC067047 or purinergic receptor antagonist suramin blunted flow/pressure-evoked vasoconstriction, whereas K ϩ and 20-HETE signaling blockade showed no effect. Importantly, we found TRPV4 channel expression to be restricted to astrocytes and not the endothelium of PA. We present evidence for a novel role of astrocytes in PA flow/pressure-evoked vasoconstriction. Our data suggest that astrocytic TRPV4 channels are key molecular sensors of hemodynamic stimuli and that a purinergic, glial-derived signal contributes to flow/pressure-induced adjustments in PA tone. Together our results support bidirectional signaling within the neurovascular unit and astrocytes as key modulators of PA tone.

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“…injected to activate TRPV4 in vivo [25, 26]. Here, the TRPV4 agonist GSK1016790A was injected (icv.)…”

Section: Methodsmentioning

confidence: 99%

Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (I_Gly) and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased I_Gly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in I_Gly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in I_Gly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

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Stimulation of transient receptor potential vanilloid 4 channel suppresses abnormal activation of microglia induced by lipopolysaccharide

Cited by 72 publications

References 39 publications

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

Astrocyte Contributions to Flow/Pressure-Evoked Parenchymal Arteriole Vasoconstriction

Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

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