Transient receptor potential vanilloid 4 is involved in the upregulation of connexin expression following pilocarpine-induced status epilepticus in mice

Men, Chen; Wang, Zhouqing; Zhou, Li; Qi, Mengwen; An, Dong Sung; Xu, Weixing; Yu, Zhan; Chen, Lei

doi:10.1016/j.brainresbull.2019.07.004

Cited by 18 publications

(26 citation statements)

References 31 publications

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“…There is evidence that TRPV4 is likely involved in the pathogenesis of epilepsy. The expression of TRPV4 increased in TLE mice, and blockage of TRPV4 markedly blocked the changes in connexion 43 and neuronal death in TLE mice [21,22]. Altered expressions of Kv4.2, the largeconductance Ca-activated K channels, and the small-conductance Ca-activated K channels have been reported in pilocarpine model of TLE [42,43,44].…”

Section: Discussionmentioning

confidence: 88%

“…After 30 min, pilocarpine (300 mg/kg, ip.) was injected to induce status epilepticus (SE) [21,22]. Seizure behavioural severity was rated using the Racine scale, as follows: category 1, immobility and facial twitch; category 2, head nodding; category 3, forelimb clonus; category 4, rearing; and category 5, rearing and falling.…”

Section: Pise Preparationmentioning

confidence: 99%

“…(1 µM/mouse) or HC-067047 (10 µM/mouse) was injected once daily for 3 consecutive days. To block TRPV4 in PISE mice, HC-067047 was injected 1 h after SE was terminated and then injected once daily for 3 d. The doses of GSK1016790A and HC-067047 were chosen as reported previously [21,22]. Control mice were administered an equal volume of vehicle.…”

Section: Drug Treatmentmentioning

confidence: 99%

“…Kv1.2 was signi cantly downregulated in autosomal dominant lateral temporal epilepsy [20]. In recent studies, the involvement of TRPV4 in the pathogenesis of epilepsy has been reported [21,22]. TRPV4 expression was found to be increased by pilocarpine-induced status epilepticus (PISE) [21].…”

Section: Introductionmentioning

confidence: 99%

“…In recent studies, the involvement of TRPV4 in the pathogenesis of epilepsy has been reported [21,22]. TRPV4 expression was found to be increased by pilocarpine-induced status epilepticus (PISE) [21]. Blockage of TRPV4 could inhibit hyperthermia-induced seizures in the larval zebra sh forebrain [23].…”

Section: Introductionmentioning

confidence: 99%

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Effect of transient receptor potential vanilloid 4 activation on the delayed rectifier potassium current in the hippocampal pyramidal neurons and Kv subunit expression in the hippocampi of mice

Zhou

et al. 2020

Preprint

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Activation of transient receptor potential vanilloid 4 (TRPV4) can increase hippocampal neuronal excitability. Recent studies have reported that TRPV4 may be involved in the pathogenesis of epilepsy. Voltage-gated potassium channels (VGPCs) play an important role in regulating neuronal excitability and abnormal VGPCs expression or function is related to epilepsy. Activation of TRPV4 can modulate ion channels, but whether activation of it could modulate VGPCs in hippocampal neurons remains unknown. Here we examined the effect of TRPV4 activation on the delayed rectifier potassium current (IK) in the hippocampal pyramidal neurons and on the Kv subunits expression. We also explored the role of TRPV4 in changes in Kv subunits expression in mice following pilocarpine-induced status epilepticus (PISE). Application of TRPV4 agonists, GSK1016790A and 5,6-EET, markedly reduced IK in the hippocampal pyramidal neurons, shifted the voltage-dependent inactivation curve to the hyperpolarization direction, and had no effect on the voltage-dependent activation curve. GSK1016790A- and 5,6-EET-induced inhibition of IK was blocked by TRPV4 specific antagonists, HC-067047 and RN1734. GSK1016790A-induced inhibition of IK was markedly attenuated by calcium/calmodulin-dependent kinase II (CaMKII) antagonist, but was not affected by protein kinase C or protein kinase A antagonists. Application of GSK1016790A for up to 1 h did not change the hippocampal protein levels of Kv1.1, Kv1.2, or Kv2.1. Intracerebroventricular injection of GSK1016790A for 3 d reduced the hippocampal protein levels of Kv1.2 and Kv2.1, leaving that of Kv1.1 unchanged. Kv1.2 and Kv2.1 protein levels were reduced markedly in hippocampi on day 3 post PISE, which was significantly reversed by HC-067047. We conclude that activation of TRPV4 inhibits IK in the hippocampal pyramidal neurons, possibly by activating CaMKII. Persistent activation of TRPV4 decreased Kv1.2 and Kv2.1 expression, which may be associated with the decrease in Kv1.2 and Kv2.1 expression following PISE.

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Section: Discussionmentioning

confidence: 88%

Section: Pise Preparationmentioning

confidence: 99%

Section: Drug Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of transient receptor potential vanilloid 4 activation on the delayed rectifier potassium current in the hippocampal pyramidal neurons and Kv subunit expression in the hippocampi of mice

Zhou

et al. 2020

Preprint

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N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

Kolić,

Kovarik

2024

BioFactors

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Acute organophosphorus compound (OP) poisoning induces symptoms of the cholinergic crises with the occurrence of severe epileptic seizures. Seizures are induced by hyperstimulation of the cholinergic system, but are enhanced by hyperactivation of the glutamatergic system. Overstimulation of muscarinic cholinergic receptors by the elevated acetylcholine causes glutamatergic hyperexcitation and an increased influx of Ca2+ into neurons through a type of ionotropic glutamate receptors, N‐methyl‐d‐aspartate (NMDA) receptors (NMDAR). These excitotoxic signaling processes generate reactive oxygen species, oxidative stress, and activation of the neuroinflammatory response, which can lead to recurrent epileptic seizures, neuronal cell death, and long‐term neurological damage. In this review, we illustrate the NMDAR structure, complexity of subunit composition, and the various receptor properties that change accordingly. Although NMDARs are in normal physiological conditions important for controlling synaptic plasticity and mediating learning and memory functions, we elaborate the detrimental role NMDARs play in neurotoxicity of OPs and focus on the central role NMDAR inhibition plays in suppressing neurotoxicity and modulating the inflammatory response. The limited efficacy of current medical therapies for OP poisoning concerning the development of pharmacoresistance and mitigating proinflammatory response highlights the importance of NMDAR inhibitors in preventing neurotoxic processes and points to new avenues for exploring therapeutics for OP poisoning.

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Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

Wang

et al. 2021

Journal Cellular Physiology

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The rapidly inactivating potassium current (I A ) is important in controlling neuronal action potentials. Altered I A function and K + channel expression have been found in epilepsy, and activation of the transient receptor potential vanilloid 4 (TRPV4) channel is involved in epilepsy pathogenesis. This study examined whether TRPV4 affects Kv4.2 and K + channel interacting protein (KCHIP) expression and I A changes following pilocarpine-induced status epilepticus (PISE) in mice. Herein, hippocampal protein levels of Kv4.2 and KCHIP2 increased 3 h-3 d and decreased 7-30 d; that of KCHIP1 increased 3-24 h and decreased 3-30 d post-PISE. The TRPV4 antagonist HC-067047 attenuated the increased protein levels of Kv4.2 and KCHIP2 but not that of KCHIP1 post-PISE. The TRPV4 agonist GSK1016790A increased hippocampal protein levels of Kv4.2 and KCHIP2 but had no effect on KCHIP1 expression. HC-067047 attenuated the increased I A in hippocampal pyramidal neurons 24 h and 3 d post-PISE. GSK1016790A increased I A in hippocampal pyramidal neurons, shifting the voltage-dependent inactivation curve toward depolarization. The GSK1016790A-induced increase of I A was blocked by protein kinase A and calcium/ calmodulin-dependent kinase II antagonists but was unaffected by protein kinase C antagonists. We conclude that TRPV4 activation may be responsible for the increases of Kv4.2 and KCHIP2 expression in hippocampi and I A in hippocampal pyramidal neurons in PISE mice, which are likely compensatory measures for hyperexcitability at the early stage of epilepsy.hippocampus, K + channel interacting protein, pilocarpine-induced status epilepticus rapidly inactivating potassium channel, transient receptor potential vanilloid 4

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Transient receptor potential vanilloid 4 is involved in the upregulation of connexin expression following pilocarpine-induced status epilepticus in mice

Cited by 18 publications

References 31 publications

Effect of transient receptor potential vanilloid 4 activation on the delayed rectifier potassium current in the hippocampal pyramidal neurons and Kv subunit expression in the hippocampi of mice

Effect of transient receptor potential vanilloid 4 activation on the delayed rectifier potassium current in the hippocampal pyramidal neurons and Kv subunit expression in the hippocampi of mice

N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

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