Regulation of two-pore-domain potassium TREK channels and their involvement in pain perception and migraine

Prado, Pablo Ávalos; Chassot, Anne-Amandine; Landra-Willm, Arnaud; Sandoz, Guillaume

doi:10.1016/j.neulet.2022.136494

Cited by 10 publications

(13 citation statements)

References 55 publications

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“…Among them, TREK‐1 channels, a type of voltage‐insensitive K2P channel, are highly expressed in the cerebral cortex, basal ganglia, hippocampus and hypothalamus (Duprat et al, 2000). Previous studies have shown the involvement of TREK‐1 in neurological disorders such as depression, migraine, epilepsy and PD (Aggarwal et al, 2021; Avalos Prado et al, 2022; Mazella et al, 2010). We found that the TREK‐1 channel coupled with the downstream of H 1 R, which mediated the inward current in LGP PV neurons, and pharmacologically blocking or genetically knocking out the TREK‐1 channel increased the intrinsic excitability and promoted the motor behaviour of mice.…”

Section: Discussionmentioning

confidence: 99%

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

Shen

Peng

et al. 2023

British J Pharmacology

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Background and Purpose Parvalbumin (PV)‐positive neurons are a type of neuron in the lateral globus pallidus (LGP) which plays an important role in motor control. The present study investigated the effect of histamine on LGPPV neurons and motor behaviour. Experimental Approach Histamine levels in LGP as well as its histaminergic innervation were determined through brain stimulation, microdialysis, anterograde tracing and immunostaining. Mechanisms of histamine action were detected by immunostaining, single‐cell qPCR, whole‐cell patch‐clamp recording, optogenetic stimulation and CRISPR/Cas9 gene‐editing techniques. The effect of histamine on motor behaviour was detected by animal behavioural tests. Key Results A direct histaminergic innervation in LGP from the tuberomammillary nucleus (TMN) and a histamine‐induced increase in the intrinsic excitability of LGPPV neurons were determined by pharmacological blockade or by genetic knockout of the histamine H1 receptor (H1R)‐coupled TWIK‐related potassium channel‐1 (TREK‐1) and the small‐conductance calcium‐activated potassium channel (SK3), as well as by activation or overexpression of the histamine H2 receptor (H2R)‐coupled hyperpolarization‐activated cyclic nucleotide‐gated channel (HCN2). Histamine negatively regulated the STN → LGPGlu transmission in LGPPV neurons via the histamine H3 receptor (H3R), whereas blockage or knockout of H3R increased the intrinsic excitability of LGPPV neurons. Conclusions and Implications Our results indicated that the endogenous histaminergic innervation in the LGP can bidirectionally promote motor control by increasing the intrinsic excitability of LGPPV neurons through postsynaptic H1R and H2R, albeit its action was negatively regulated by the presynaptic H3R, thereby suggesting possible role of histamine in motor deficits manifested in Parkinson's disease (PD).

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Section: Discussionmentioning

confidence: 99%

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

Shen

Peng

et al. 2023

British J Pharmacology

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“…TREK channels are polymodal sensors regulated by mechanical, thermal, and chemical stimuli 16,23,27,30,31,36,56-66 (Figure) and can dynamically interconvert between different opening states in response to these stimuli. 57 Mechanical gating of these channels is related to structural transformations triggered by tension of the lipid bilayer and involving interaction with membrane phospholipids.…”

Section: K2p Channels In Nociceptorsmentioning

confidence: 99%

“…These studies also suggest that activation of TREK and TRESK channels may provide a therapeutic target to treat pain. 6,16,94,95 For example, preventing PKA or PKC mediated phosphorylation may promote TREK channel activity 67 and may contribute to the analgesic effects of activation of GABA B and mu-opioid receptors. 70,74,75 TREK1 has been shown to contribute of morphine-induced analgesia in experimental mouse models of neuropathic pain.…”

Section: Perspectivementioning

confidence: 99%

“…14 Given their importance in pain modulation, voltage-gated K + channels (K v ) and 2-pore domain K + channels (K2P) are potential targets for designing novel analgesic compounds. 6,[14][15][16][17] This review will focus on K2P channels, which are multimodal sensors that may have an important role in several pain disorders, including neuropathic pain and migraine 6,[15][16][17][18][19][20]…”

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confidence: 99%

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What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

Benarroch

2022

Neurology

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Nociceptive dorsal root ganglion (DRG) and trigeminal neurons express a large numbers of ion channels that determine their threshold and responses to both noxious and innocuous stimuli.1 Several voltage-gated sodium channels (Nav),2 voltage-gated calcium (Ca2+) channels,3 transient receptor potential (TRP) channels,4 and other cation channels increase nociceptor responsiveness, whereas a variety of potassium (K+) channels prevent spontaneous nociceptor activity and reduce their firing probability.5-9 The imbalance between these 2 opposing influences, which may occur as a consequence of channel gene sequence variants,10 effect of inflammatory mediators,11 or transcriptional dysregulation,12,13 promotes neuropathic pain, hyperalgesia, and allodynia.14 Given their importance in pain modulation, voltage-gated K+ channels (Kv) and 2-pore domain K+ channels (K2P) are potential targets for designing novel analgesic compounds.6,14-17 This review will focus on K2P channels, which are multimodal sensors that may have an important role in several pain disorders, including neuropathic pain and migraine6,15-20

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“…We have already published several papers [19][20][21][22] from GDS2678[23] by integrating microarray signi cance analysis (SAM) [24], SPSS correlation coe cient Pearson and gene (protein) reconstruction network (GRNInfer) [25] mutual positive veri cation. GPR68-activated subnetwork we identi ed includes upstream ATP2B1, ITPR1, KCNK1, SSTR2, feedback MAP1B_1, MAP1B_2, ZNF91_2, downstream NDRG4, NPAL3, PDE4DIP, SEL1L, SPTB, TUBGCP4_1, TUBGCP4_2.…”

Section: Introductionmentioning

confidence: 99%

GPR68 activated transmembrane to cytosol growth-based visual learning based on Prefrontal Cortex big data

Wang

Hong

Cui

et al. 2023

Preprint

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G protein-coupled receptor (GPR68) is widely distributed in the human body and participates in various physiological and pathological processes. The main GPR68-activated and -inhibited molecular network was constructed in Prefrontal Cortex by integrating SAM, SPSS Pearson and GRNInfer mutual positive verification based on richness. The main GPR68 activated molecular subnetwork composed of upstream KCNKpotassium ion transmembrane transport, feedback MAP1B_2-cytosol microtubule binding, and downstream NDRG4-cytosol growth-based visual learning in Prefrontal Cortex. The main GPR68 inhibited subnetwork included upstream PKP4 with TMEM63A-extracellular exosome nucleotide binding in Prefrontal Cortex by DAVID. The relationship of PKP4 activation to TMEM63A was found in Prefrontal Cortex for positive main molecular verification. The relationship of NDRG4 inhibition to TMEM63A -> KCNK1 -> PKP4 in Prefrontal Cortex for negative main molecular verification. The main GPR68-activated and -inhibited model was positive verified by the corresponding other similar and common knowledge. We put forwards the model in Prefrontal Cortex that GPR68 activated cytosol microtubule binding coupling potassium ion transmembrane transport to cytosol growth-based visual learning with 18-inhibited model for mutual negative knowledge verification. The role and mechanism of GPR68 activated transmembrane to cytosol growth-based visual learning based on Prefrontal Cortex big data contribute to better detection, evaluation, intervention, tracking, and other health management of brain diseases.

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Regulation of two-pore-domain potassium TREK channels and their involvement in pain perception and migraine

Cited by 10 publications

References 55 publications

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

GPR68 activated transmembrane to cytosol growth-based visual learning based on Prefrontal Cortex big data

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