Transient Receptor Potential Vanilloid 4-Induced Modulation of Voltage-Gated Sodium Channels in Hippocampal Neurons

Hong, Zhiwen; Jie, Pinghui; Tian, Yangchao; Chen, Tingting; Chen, Lei; Chen, Ling

doi:10.1007/s12035-014-9038-5

Cited by 11 publications

(15 citation statements)

References 44 publications

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“…In our previous studies, chronic activation of TRPV4 may change the expression of voltage-gated sodium channels and glutamate receptors [5, 37]. Here, hippocampal protein levels of GlyR α1, α2, α3 and β subunits were examined in GSK1016790A-injected mice.…”

Section: Resultsmentioning

confidence: 97%

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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Section: Resultsmentioning

confidence: 97%

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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“…β1 and β2 subunits of sodium channels are expressed endogenously in both HEK293 cells and cultured hippocampal neurons13141516. To investigate whether APP enhancecs sodium current density through modulation of either α subunit or β1/β2 subunit of Nav1.6, we co-expressed full-length APP with α subunit of Nav1.6 in Xenopus laevis oocytes, where few β1, β2 and α subunits of Nav1.6 are expressed endogenously.…”

Section: Resultsmentioning

confidence: 99%

Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway

Wang

Yang

et al. 2016

Sci Rep

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Amyloid precursor protein (APP), commonly associated with Alzheimer’s disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Nav1.6 sodium channels in Xenopus oocytes resulted in an increase in peak sodium currents, which was enhanced by constitutively active Go mutant and blocked by a dominant negative mutant. JNK and CDK5 inhibitor attenuated increases in Nav1.6 sodium currents induced by overexpression of APP. Nav1.6 sodium currents were increased by APPT668E (mutant Thr to Glu) and decreased by T668A (mutant Thr to ALa) mutant, respectively. The cell surface expression of Nav1.6 sodium channels in the white matter of spinal cord and the spinal conduction velocity is decreased in APP, p35 and JNK3 knockout mice. Therefore, APP modulates Nav1.6 sodium channels through a Go-coupled JNK pathway, which is dependent on phosphorylation of APP at Thr668.

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“…64-0817 [G85150T-3], Warner Instruments Inc., Hamden, CT, USA) were used with a resistance of 1–3 MΩ when they were filled with the pipette solution composed of (in mM) KCl 140, CaCl 2 1, MgCl 2 2, EGTA 10, HEPES 10, and Tris-ATP 5 at pH 7.3. The expression of TRPV4 receptors was functionally verified by recording the TRPV4 agonist (GSK1016790A)-activated current as previously reported (Hong et al, 2016). …”

Section: Methodsmentioning

confidence: 96%

“…D-Sphingosine, H-89, PKI, LY294002, KN62, and KN93 were present in the pipette solution and pre-applied by dialyzing into the neurons through the pipette. The concentrations of these drugs were chosen according to previous reports (Ben-Ari et al, 1997; Williams and Doherty, 1999; Chen et al, 2000, 2008b; Liu et al, 2007; Langelueddecke et al, 2012; Sisignano et al, 2012; Li et al, 2013a; Shen et al, 2014; Hong et al, 2016; Rahman et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

“…In the central nervous system (CNS), activation of TRPV4 by body temperature regulates the resting membrane potential in hippocampal neurons (Shibasaki et al, 2007). Although chronic activation of TRPV4 may increase the expression of the α subunits of voltage-gated sodium channels, acute application of a TRPV4 agonist inhibits the voltage-gated sodium current in hippocampal pyramidal neurons (Hong et al, 2016). In the CNS, the balance between the excitatory and inhibitory neurotransmitter systems is crucial for modulating neuronal excitability.…”

Section: Introductionmentioning

confidence: 99%

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Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

Hong

Tian

et al. 2016

Front. Mol. Neurosci.

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The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (IGABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK) and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited IGABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K) agonist. GSK1016790A-induced inhibition of IGABA was also significantly attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation.

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Transient Receptor Potential Vanilloid 4-Induced Modulation of Voltage-Gated Sodium Channels in Hippocampal Neurons

Cited by 11 publications

References 44 publications

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

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

Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway

Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

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