Tandem pore TWIK-related potassium channels and neuroprotection

Lamas, José Antonio; Fernández-Fernández, Diego

doi:10.4103/1673-5374.253506

Cited by 21 publications

(14 citation statements)

References 158 publications

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“…Delayed rectified potassium voltage-gated channels, Kcnc2 and Kcng2 , play key roles in action potential shaping and consequently in nociception transmission and pain plasticity 45 . Kcnk1 8, a TWIK-related two-pore potassium channel is involved in regulating the resting membrane potential 68 , 69 and has been linked to migraine with aura pathogenesis 70 , 71 . Finally, we identified higher expression of Trpv4 in female TG sensory neuronal fractions and this ion channel plays an important role in pain sensitization that has been thoroughly studied 47 , 72 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic sex differences in sensory neuronal populations of mice

Mecklenburg

Zou

Wangzhou

et al. 2020

Sci Rep

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Many chronic pain conditions show sex differences in their epidemiology. This could be attributed to sex-dependent differential expression of genes (DEGs) involved in nociceptive pathways, including sensory neurons. This study aimed to identify sex-dependent DEGs in estrous female versus male sensory neurons, which were prepared by using different approaches and ganglion types. RNA-seq on non-purified sensory neuronal preparations, such as whole dorsal root ganglion (DRG) and hindpaw tissues, revealed only a few sex-dependent DEGs. Sensory neuron purification increased numbers of sex-dependent DEGs. These DEG sets were substantially influenced by preparation approaches and ganglion types [DRG vs trigeminal ganglia (TG)]. Percoll-gradient enriched DRG and TG neuronal fractions produced distinct sex-dependent DEG groups. We next isolated a subset of sensory neurons by sorting DRG neurons back-labeled from paw and thigh muscle. These neurons have a unique sex-dependent DEG set, yet there is similarity in biological processes linked to these different groups of sex-dependent DEGs. Female-predominant DEGs in sensory neurons relate to inflammatory, synaptic transmission and extracellular matrix reorganization processes that could exacerbate neuro-inflammation severity, especially in TG. Male-selective DEGs were linked to oxidative phosphorylation and protein/molecule metabolism and production. Our findings catalog preparation-dependent sex differences in neuronal gene expressions in sensory ganglia.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic sex differences in sensory neuronal populations of mice

Mecklenburg

Zou

Wangzhou

et al. 2020

Sci Rep

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“…TWIK-related K + channels (TREK-1, TREK-2, and TRAAK) are a mechano-gated subclass of K 2P channels, and are highly expressed throughout the nervous system (Talley et al, 2001) as well as in several nonneuronal tissues including cardiac and smooth muscles (Gurney and Manoury, 2009;Schmidt et al, 2014;Ma et al, 2018). TREK-1 in particular plays a central role in pain perception, neuroprotection, and cardiac rhythmogenesis (Alloui et al, 2006;Wiedmann et al, 2016;Lamas and Fernandez-Fernandez, 2019) and is considered a viable therapeutic target for treating depression (Heurteaux et al, 2006), atrial fibrillation (Lugenbiel et al, 2017), and hypermotility disorders of the gastrointestinal tract (Ma et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels

Lewis

2020

Front. Pharmacol.

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TREK-1 channel activity is a critical regulator of neuronal, cardiac, and smooth muscle physiology and pathology. The antidepressant peptide, spadin, has been proposed to be a TREK-1-specific blocker. Here we sought to examine the mechanism of action underlying spadin inhibition of TREK-1 channels. Heterologous expression in Xenopus laevis oocytes and electrophysiological analysis using two-electrode voltage clamp in standard bath solutions was used to characterize the pharmacological profile of wild-type and mutant murine TREK-1 and TREK-2 channels using previously established human K 2P activators; arachidonic acid (AA), cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), BL-1249, and cinnamyl-3,4-dihydroxy-a-cyanocinnamate (CDC) and inhibitors; spadin and barium (Ba 2+). Mouse TREK-1 and TREK-2 channel currents were both significantly increased by AA, BL-1249, and CDC, similar to their human homologs. Under basal conditions, both TREK-1 and TREK-2 currents were insensitive to application of spadin, but could be blocked by Ba 2+. Spadin did not significantly inhibit either TREK-1 or TREK-2 currents either chemically activated by AA, BL-1249, or CDC, or structurally activated via a gating mutation. However, pre-exposure to spadin significantly perturbed the subsequent activation of TREK-1 currents by AA, but not TREK-2. Furthermore, spadin was unable to prevent activation of TREK-1 by BL-1249, CDC, or the related bioactive lipid, DHA. Spadin specifically antagonizes the activation of TREK-1 channels by AA, likely via an allosteric mechanism. Lack of intrinsic activity may explain the absence of clinical side effects during antidepressant therapy.

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“…Concerning the K 2P channels, the presence of these channels in HUA is uncertain, and only Martin et al (2014) have reported the presence of mRNA from the TREK-1 and TRAAK channels. Increasing evidence shows a role for TREK channels in cardiac pathologies such as atrial fibrillation and heart failure [ 202 , 203 , 204 ]. TREK-1 channel openers include riluzole, chloroform, and diethyl ether.…”

Section: Clinical Importance and Medical Uses Of K + mentioning

confidence: 99%

Clinical Importance of the Human Umbilical Artery Potassium Channels

Lorigo

Oliveira

2020

Cells

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Potassium (K+) channels are usually predominant in the membranes of vascular smooth muscle cells (SMCs). These channels play an important role in regulating the membrane potential and vessel contractility—a role that depends on the vascular bed. Thus, the activity of K+ channels represents one of the main mechanisms regulating the vascular tone in physiological and pathophysiological conditions. Briefly, the activation of K+ channels in SMC leads to hyperpolarization and vasorelaxation, while its inhibition induces depolarization and consequent vascular contraction. Currently, there are four different types of K+ channels described in SMCs: voltage-dependent K+ (KV) channels, calcium-activated K+ (KCa) channels, inward rectifier K+ (Kir) channels, and 2-pore domain K+ (K2P) channels. Due to the fundamental role of K+ channels in excitable cells, these channels are promising therapeutic targets in clinical practice. Therefore, this review discusses the basic properties of the various types of K+ channels, including structure, cellular mechanisms that regulate their activity, and new advances in the development of activators and blockers of these channels. The vascular functions of these channels will be discussed with a focus on vascular SMCs of the human umbilical artery. Then, the clinical importance of K+ channels in the treatment and prevention of cardiovascular diseases during pregnancy, such as gestational hypertension and preeclampsia, will be explored.

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Tandem pore TWIK-related potassium channels and neuroprotection

Cited by 21 publications

References 158 publications

Transcriptomic sex differences in sensory neuronal populations of mice

Transcriptomic sex differences in sensory neuronal populations of mice

Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels

Clinical Importance of the Human Umbilical Artery Potassium Channels

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