TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures

Huang, Weiyuan; Ke, Yue; Zhu, Jianping; Liu, Shuai; Cong, Jin; Ye, Hailin; Guo, Yanwu; Wang, Kewan; Zhang, Zhenhai; Meng, Wenxiang; Gao, Tianming; Luhmann, Heiko J.; Kilb, Werner; Chen, Rongqing

doi:10.1016/j.celrep.2021.109404

Cited by 14 publications

(16 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed that 70 (76.9%) mice showed SE without death, 15 mice (16.5%) did not show SE, and 6 (6.6%) mice had died in 2 h following pilocarpine treatment ( Figure 1B ). This is consistent with our previous studies ( 10 , 11 ). The survival mice with SE were randomly allocated into 3 groups that were i.p.…”

Section: Resultssupporting

confidence: 94%

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

et al. 2022

Self Cite

View full text Add to dashboard Cite

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.

show abstract

Section: Resultssupporting

confidence: 94%

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since migraine shares genetic as well as pathophysiological features with other episodic neurological disorders, influence of TRESK function on epileptic seizures was examined as well (Fig. 4C) [96]. Seizures result from neuronal hyperexcitability, which is associated with sustained neuronal depolarization and uncontrolled generation of APs [96].…”

Section: Diseases and Pathophysiological Conditions Associated With T...mentioning

confidence: 99%

“…4C) [96]. Seizures result from neuronal hyperexcitability, which is associated with sustained neuronal depolarization and uncontrolled generation of APs [96]. In vivo, seizure episodes are self-limiting and followed by a period of suppressed cortical activity, that is induced by depolarization-induced shunting inhibition (DShI) [96].…”

Section: Diseases and Pathophysiological Conditions Associated With T...mentioning

confidence: 99%

“…Seizures result from neuronal hyperexcitability, which is associated with sustained neuronal depolarization and uncontrolled generation of APs [96]. In vivo, seizure episodes are self-limiting and followed by a period of suppressed cortical activity, that is induced by depolarization-induced shunting inhibition (DShI) [96]. DShI can suppress uncontrolled AP generation by membrane repolarization through activation of K + channels as well as inhibition of postsynaptic ionotropic receptors [96].…”

Section: Diseases and Pathophysiological Conditions Associated With T...mentioning

confidence: 99%

“…In vivo, seizure episodes are self-limiting and followed by a period of suppressed cortical activity, that is induced by depolarization-induced shunting inhibition (DShI) [96]. DShI can suppress uncontrolled AP generation by membrane repolarization through activation of K + channels as well as inhibition of postsynaptic ionotropic receptors [96]. Electrophysiological analysis of hippocampal CA3 neurons from TRESK knockout mice confirmed a contribution of TRESK to the DShI, consistent with prolonged and severe seizure attacks observed in knockout mice as well as attenuated severity in mice overexpressing TRESK (Fig.…”

Section: Diseases and Pathophysiological Conditions Associated With T...mentioning

confidence: 99%

See 2 more Smart Citations

The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel

Schreiber

Düfer

Seebohm

2022

Cell Physiol Biochem

View full text Add to dashboard Cite

The TWIK-related spinal cord K+ channel (TRESK) is part of the two-pore domain K+ channel family (K2P), which are also called leak potassium channels. As indicated by the channel family name, TRESK conducts K+ ions along the concentration gradient in a nearly voltage-independent manner leading to lowered membrane potentials. Although functional and pharmacological similarities exist, TRESK shows low sequence identity with other K2P channels. Moreover, the channel possesses several unique features such as its sensitivity to intracellular Ca2+ ions, that are not found in other K2P channels. High expression rates are found in immune-associated and neuronal cells, especially in sensory neurons of the dorsal root and trigeminal ganglia. As a consequence of the induced hyperpolarization, TRESK influences neuronal firing, the release of inflammatory mediators and the proliferation of distinct immune cells. Consequently, this channel might be a suitable target for pharmacological intervention in migraine, epilepsy, neuropathic pain or distinct immune diseases. In this review, we summarize the biochemical and biophysical properties of TRESK channels as well as their sensitivity to different known compounds. Furthermore, we give a structured overview about the physiological and pathophysiological impact of TRESK, that render the channel as an interesting target for specific drug development.

show abstract

Implantable probe with integrated reference electrode for in situ neural signal and calcium ion monitoring

Xiao,

Xu,

Wang

et al. 2024

Bio-des. Manuf.

View full text Add to dashboard Cite

TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures

Cited by 14 publications

References 104 publications

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

The Special One: Architecture, Physiology and Pharmacology of the TRESK Channel

Implantable probe with integrated reference electrode for in situ neural signal and calcium ion monitoring

Contact Info

Product

Resources

About