Relevant bibliographies by topics / Tandem Pore Domain Potassium Channels

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Academic literature on the topic 'Tandem Pore Domain Potassium Channels'

Author: Grafiati
Published: 4 June 2021
Last updated: 11 February 2022

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Journal articles on the topic "Tandem Pore Domain Potassium Channels"

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Kindler, Christoph H., Spencer C. Yost, and Andrew T. Gray. "Local Anesthetic Inhibition of Baseline Potassium Channels with Two Pore Domains in Tandem." Anesthesiology 90, no. 4 (April 1, 1999): 1092–102. http://dx.doi.org/10.1097/00000542-199904000-00024.

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Background Recently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels. Methods Oocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1, and TWIK-1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two-electrode voltage-clamp and current-clamp techniques. Results Bupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA-injected oocytes compared with saline-injected control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine 31+/-7 mV vs. 6+/-4 mV). Conclusions Local anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.
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Gray, Andrew T., Byron B. Zhao, Christoph H. Kindler, Bruce D. Winegar, Matthew J. Mazurek, Jie Xu, Raymond A. Chavez, John R. Forsayeth, and C. Spencer Yost. "Volatile Anesthetics Activate the Human Tandem Pore Domain Baseline K+Channel KCNK5." Anesthesiology 92, no. 6 (June 1, 2000): 1722–30. http://dx.doi.org/10.1097/00000542-200006000-00032.

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Background Previous studies have identified a volatile anesthetic-induced increase in baseline potassium permeability and concomitant neuronal inhibition. The emerging family of tandem pore domain potassium channels seems to function as baseline potassium channels in vivo. Therefore, we studied the effects of clinically used volatile anesthetics on a recently described member of this family. Methods A cDNA clone containing the coding sequence of KCNK5 was isolated from a human brain library. Expression of KCNK5 in the central nervous system was determined by Northern blot analysis and reverse-transcription polymerase chain reaction. Functional expression of the channel was achieved by injection of cRNA into Xenopus laevis oocytes. Results Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord. When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30%. Conclusion Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia.
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Bryan, Robert M., Junping You, Sharon C. Phillips, Jon J. Andresen, Eric E. Lloyd, Paul A. Rogers, Stuart E. Dryer, and Sean P. Marrelli. "Evidence for two-pore domain potassium channels in rat cerebral arteries." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 2 (August 2006): H770—H780. http://dx.doi.org/10.1152/ajpheart.01377.2005.

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Little is known about the presence and function of two-pore domain K+ (K2P) channels in vascular smooth muscle cells (VSMCs). Five members of the K2P channel family are known to be directly activated by arachidonic acid (AA). The purpose of this study was to determine 1) whether AA-sensitive K2P channels are expressed in cerebral VSMCs and 2) whether AA dilates the rat middle cerebral artery (MCA) by increasing K+ currents in VSMCs via an atypical K+ channel. RT-PCR revealed message for the following AA-sensitive K2P channels in rat MCA: tandem of P domains in weak inward rectifier K+ (TWIK-2), TWIK-related K+ (TREK-1 and TREK-2), TWIK-related AA-stimulated K+ (TRAAK), and TWIK-related halothane-inhibited K+ (THIK-1) channels. However, in isolated VSMCs, only message for TWIK-2 was found. Western blotting showed that TWIK-2 is present in MCA, and immunohistochemistry further demonstrated its presence in VSMCs. AA (10–100 μM) dilated MCAs through an endothelium-independent mechanism. AA-induced dilation was not affected by inhibition of cyclooxygenase, epoxygenase, or lipoxygenase or inhibition of classical K+ channels with 10 mM TEA, 3 mM 4-aminopyridine, 10 μM glibenclamide, or 100 μM Ba2+. AA-induced dilations were blocked by 50 mM K+, indicating involvement of a K+ channel. AA (10 μM) increased whole cell K+ currents in dispersed cerebral VSMCs. AA-induced currents were not affected by inhibitors of the AA metabolic pathways or blockade of classical K+ channels. We conclude that AA dilates the rat MCA and increases K+ currents in VSMCs via an atypical K+ channel that is likely a member of the K2P channel family.
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Lengyel, Miklós, Gábor Czirják, David A. Jacobson, and Péter Enyedi. "TRESK and TREK-2 two-pore-domain potassium channel subunits form functional heterodimers in primary somatosensory neurons." Journal of Biological Chemistry 295, no. 35 (July 7, 2020): 12408–25. http://dx.doi.org/10.1074/jbc.ra120.014125.

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Two-pore-domain potassium channels (K2P) are the major determinants of the background potassium conductance. They play a crucial role in setting the resting membrane potential and regulating cellular excitability. These channels form homodimers; however, a few examples of heterodimerization have also been reported. The K2P channel subunits TRESK and TREK-2 provide the predominant background potassium current in the primary sensory neurons of the dorsal root and trigeminal ganglia. A recent study has shown that a TRESK mutation causes migraine because it leads to the formation of a dominant negative truncated TRESK fragment. Surprisingly, this fragment can also interact with TREK-2. In this study, we determined the biophysical and pharmacological properties of the TRESK/TREK-2 heterodimer using a covalently linked TRESK/TREK-2 construct to ensure the assembly of the different subunits. The tandem channel has an intermediate single-channel conductance compared with the TRESK and TREK-2 homodimers. Similar conductance values were recorded when TRESK and TREK-2 were coexpressed, demonstrating that the two subunits can spontaneously form functional heterodimers. The TRESK component confers calcineurin-dependent regulation to the heterodimer and gives rise to a pharmacological profile similar to the TRESK homodimer, whereas the presence of the TREK-2 subunit renders the channel sensitive to the selective TREK-2 activator T2A3. In trigeminal primary sensory neurons, we detected single-channel activity with biophysical and pharmacological properties similar to the TRESK/TREK-2 tandem, indicating that WT TRESK and TREK-2 subunits coassemble to form functional heterodimeric channels also in native cells.
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Smith, Howard. "Calcineurin as a Nociceptor Modulator." Pain Physician 4;12, no. 4;7 (July 14, 2009): E309—E318. http://dx.doi.org/10.36076/ppj.2009/12/e09.

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Calcineurin may be involved in affecting nociceptive processes in multiple circumstances. It is conceivable that interfering with calcineurin’s normal role in contributing to glial resting membrane potential, via its effects on the ion channel (TRESK) [tandem-pore-domain weakly inward rectifying potassium channels (TWIK)-related spinal cord potassium channels] may facilitate nociception. Another aspect of calcineurin function may be its role in the pronociceptive signaling of nuclear factor of activated T-cells (NFAT). NFAT activation via mediators (e.g. Substance P, brain-derived neurotrophic factor, nerve growth factor, bradykinin) appears to be dependent on calcineurin function. This calcineurin-regulated NFAT signaling may subsequently lead to transcription of pronociceptive genes as well as upregulation of pronociceptive chemokine receptors in the dorsal root ganglion. In fact, multiple articles have described the clinical use of calcineurin-inhibitors leading to pain, a phenomenon referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Thus, it appears that calcineurin functions may encompass actions which promote or dampen nociceptive processes. A greater understanding of the physiology of calcineurin, especially as it relates to modulating nociception may lead to the development of novel analgesic targets in attempts to optimally alleviate patient discomfort. Key words: Pain, neuropathic, calcineurin, NFAT, TRESK-[Tandem-pore-domain weakly inward rectifying potassium channels (TWIK)-related spinal cord potassium channels], CIPS (calcineurin-induced pain syndrome)
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Noto, Federico, Sandra Recuero, Julián Valencia, Beatrice Saporito, Domenico Robbe, Sergi Bonet, Augusto Carluccio, and Marc Yeste. "Inhibition of Potassium Channels Affects the Ability of Pig Spermatozoa to Elicit Capacitation and Trigger the Acrosome Exocytosis Induced by Progesterone." International Journal of Molecular Sciences 22, no. 4 (February 17, 2021): 1992. http://dx.doi.org/10.3390/ijms22041992.

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During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial for capacitation of mouse and human sperm, their role in pigs has not been investigated. With this purpose, sperm samples from 15 boars were incubated in capacitation medium for 300 min with quinine, a general blocker of potassium channels (including voltage-gated potassium channels, calcium-activated potassium channels, and tandem pore domain potassium channels), and paxilline (PAX), a specific inhibitor of calcium-activated potassium channels. In all samples, acrosome exocytosis was induced after 240 min of incubation with progesterone. Plasma membrane and acrosome integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and total and progressive sperm motility were evaluated after 0, 120, and 240 min of incubation, and after 5, 30, and 60 min of progesterone addition. Although blocking potassium channels with quinine and PAX prevented sperm to elicit in vitro capacitation by impairing motility and mitochondrial function, as well as reducing intracellular calcium levels, the extent of that inhibition was larger with quinine than with PAX. Therefore, while our data support that calcium-activated potassium channels are essential for sperm capacitation in pigs, they also suggest that other potassium channels, such as the voltage-gated, tandem pore domain, and mitochondrial ATP-regulated ones, are involved in that process. Thus, further research is needed to elucidate the specific functions of these channels and the mechanisms underlying its regulation during sperm capacitation.
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Skatchkov, S. N., M. J. Eaton, Y. M. Shuba, Y. V. Kucheryavykh, C. Derst, R. W. Veh, A. Wurm, et al. "Tandem-pore domain potassium channels are functionally expressed in retinal (Müller) glial cells." Glia 53, no. 3 (2005): 266–76. http://dx.doi.org/10.1002/glia.20280.

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Blin, Sandy, Ismail Ben Soussia, Eun-Jin Kim, Frédéric Brau, Dawon Kang, Florian Lesage, and Delphine Bichet. "Mixing and matching TREK/TRAAK subunits generate heterodimeric K2P channels with unique properties." Proceedings of the National Academy of Sciences 113, no. 15 (March 28, 2016): 4200–4205. http://dx.doi.org/10.1073/pnas.1522748113.

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The tandem of pore domain in a weak inwardly rectifying K+ channel (Twik)-related acid-arachidonic activated K+ channel (TRAAK) and Twik-related K+ channels (TREK) 1 and TREK2 are active as homodimers gated by stretch, fatty acids, pH, and G protein-coupled receptors. These two-pore domain potassium (K2P) channels are broadly expressed in the nervous system where they control excitability. TREK/TRAAK KO mice display altered phenotypes related to nociception, neuroprotection afforded by polyunsaturated fatty acids, learning and memory, mood control, and sensitivity to general anesthetics. These channels have emerged as promising targets for the development of new classes of anesthetics, analgesics, antidepressants, neuroprotective agents, and drugs against addiction. Here, we show that the TREK1, TREK2, and TRAAK subunits assemble and form active heterodimeric channels with electrophysiological, regulatory, and pharmacological properties different from those of homodimeric channels. Heteromerization occurs between all TREK variants produced by alternative splicing and alternative translation initiation. These results unveil a previously unexpected diversity of K2P channels that will be challenging to analyze in vivo, but which opens new perspectives for the development of clinically relevant drugs.
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Rivas-Ramírez, Paula, Antonio Reboreda, Lola Rueda-Ruzafa, Salvador Herrera-Pérez, and J. Antonio Lamas. "PIP2 Mediated Inhibition of TREK Potassium Currents by Bradykinin in Mouse Sympathetic Neurons." International Journal of Molecular Sciences 21, no. 2 (January 8, 2020): 389. http://dx.doi.org/10.3390/ijms21020389.

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Bradykinin (BK), a hormone inducing pain and inflammation, is known to inhibit potassium M-currents (IM) and to increase the excitability of the superior cervical ganglion (SCG) neurons by activating the Ca2+-calmodulin pathway. M-current is also reduced by muscarinic agonists through the depletion of membrane phosphatidylinositol 4,5-biphosphate (PIP2). Similarly, the activation of muscarinic receptors inhibits the current through two-pore domain potassium channels (K2P) of the “Tandem of pore-domains in a Weakly Inward rectifying K+ channel (TWIK)-related channels” (TREK) subfamily by reducing PIP2 in mouse SCG neurons (mSCG). The aim of this work was to test and characterize the modulation of TREK channels by bradykinin. We used the perforated-patch technique to investigate riluzole (RIL) activated currents in voltage- and current-clamp experiments. RIL is a drug used in the palliative treatment of amyotrophic lateral sclerosis and, in addition to blocking voltage-dependent sodium channels, it also selectively activates the K2P channels of the TREK subfamily. A cell-attached patch-clamp was also used to investigate TREK-2 single channel currents. We report here that BK reduces spike frequency adaptation (SFA), inhibits the riluzole-activated current (IRIL), which flows mainly through TREK-2 channels, by about 45%, and reduces the open probability of identified single TREK-2 channels in cultured mSCG cells. The effect of BK on IRIL was precluded by the bradykinin receptor (B2R) antagonist HOE-140 (d-Arg-[Hyp3, Thi5, d-Tic7, Oic8]BK) but also by diC8PIP2 which prevents PIP2 depletion when phospholipase C (PLC) is activated. On the contrary, antagonizing inositol triphosphate receptors (IP3R) using 2-aminoethoxydiphenylborane (2-APB) or inhibiting protein kinase C (PKC) with bisindolylmaleimide did not affect the inhibition of IRIL by BK. In conclusion, bradykinin inhibits TREK-2 channels through the activation of B2Rs resulting in PIP2 depletion, much like we have demonstrated for muscarinic agonists. This mechanism implies that TREK channels must be relevant for the capture of information about pain and visceral inflammation.
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Li, Zheng-Bin, Hai-Xia Zhang, Liao-Liao Li, and Xiao-Liang Wang. "Enhanced expressions of arachidonic acid-sensitive tandem-pore domain potassium channels in rat experimental acute cerebral ischemia." Biochemical and Biophysical Research Communications 327, no. 4 (February 2005): 1163–69. http://dx.doi.org/10.1016/j.bbrc.2004.12.124.

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Dissertations / Theses on the topic "Tandem Pore Domain Potassium Channels"

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Gabriel, Luke R. "Dynamic Regulation at the Neuronal Plasma Membrane: Novel Endocytic Mechanisms Control Anesthetic-Activated Potassium Channels and Amphetamine-Sensitive Dopamine Transporters: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/725.

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Endocytic trafficking dynamically regulates neuronal plasma membrane protein presentation and activity, and plays a central role in excitability and plasticity. Over the course of my dissertation research I investigated endocytic mechanisms regulating two neuronal membrane proteins: the anesthetic-activated potassium leak channel, KCNK3, as well as the psychostimulant-sensitive dopamine transporter (DAT). My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. Additionally, PKC-mediated KCNK3 trafficking requires a non-canonical endocytic motif, which is shared exclusively between KCNK3 and sodium-dependent neurotransmitter transporters, such as DAT. DAT trafficking studies in intact ex vivo adult striatal slices indicate that DAT endocytic trafficking has both dynamin-dependent and –independent components. Moreover, DAT segregates into two populations at the neuronal plasma membrane: trafficking-competent and -incompetent. Taken together, these results demonstrate that novel, non-classical endocytic mechanisms dynamically control the plasma membrane presentation of these two important neuronal proteins.
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Clarke, Catherine Elizabeth. "Characterisation of two pore domain potassium channels." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408808.

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Goonetilleke, Lakshman. "Two-pore domain potassium channels in arterial smooth muscle." Thesis, University of Liverpool, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485866.

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The membrane potential of arterial smooth cells, and consequently arterial tone, is. regulated by the activity of plasmalemmal K+ selective ion channels. K2P channels are responsible for background K+ (KB) conductances which contribute to generation of the resting membrane potential. They have been identified in arterial smooth muscle cells but their significance is poorly understood. A Ks conductance is expressed in rat femoral arterial smooth muscle cells (rFASMCs), and the aim of this project was to (i) determine the expression profile of K2P subunits in rat femoral artery and (ii) identify the molecular correlate of the KB conductance in rFASMCs. Using RT-PCR, we identified transcripts encoding TWIK-2, TASK-I, TASK-2, TREK-I, TREK-2 and THIK-I in total rat femoral artery RNA. TWIK-2, TASK-I, TASK-2 and TREK-I were further identified at the protein level in isolated FASMCs by antibody staining. Only TWIK-2 was detected at the cell surface, while TASK-I, TASK-2 and TREK-I had a predominantly intracellular localisation. Immunohistochemistry of femoral artery sections may also support the expression of TWIK-2, TASK-I and TASK-2 (but not TREK-I) in the endothelium. To allow comparison between cloned and native conductances, the open reading frames of rTWIK-2, rTASK-2 and rTREK-I were cloned by PCR amplification. The sequence encoding rTASK-2 was cloned de novo and submitted to the EBI gene data base (Accession no: AM229406). Functional expression ofrTWIK-2 and rTASK-2 was investigated in Xenopus 'laevis oocytes. rTWIK-2 did not exhibit strong expression in the Xenopus laevis expression system. Conversely, recombinant rTASK-2 channels formed K+ selective, extracellular pH sensitive ion channels. The basic pharmacological properties of cloned rTASK-2 channels were also investigated. Currents were insensitive to extracellular TEA, 4-AP and Cs+, but were sensitive to inhibition by Ba2+, Zn2+and quinidine. Inhibition by extracellular Ba2+was strongly time and voltage-dependent. Ba2+ inhibition of rTASK-2 was characterised by steady-state analysis and voltage pulses. Although we were unable to describe the functional correlate of the KB conductance in rFASMCs, this thesis has established the groundwork for further correlative studies. The information provided will assist in the identification of native TASK-2 conductances.
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Evans, Louisa-Jane Ping Ping. "Pharmacological and functional regulation of two-pore domain potassium channels." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501442.

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Gallagher, Anne Wendy. "The expression of two-pore domain potassium channels in osteoblastic cells." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526865.

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Robledo-Zapico, Christian J. "The role of two-pore domain potassium channels in anaesthesia and sleep." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497747.

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Walsh, Yvonne. "Pharmacological regulation of TREK1, TREK2 and TRESK two pore domain potassium channels." Thesis, University of Kent, 2017. https://kar.kent.ac.uk/68081/.

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Introduction: Two pore domain potassium (K2P) channels are responsible for background currents that regulate membrane potential and neuronal excitability. Compounds which alter the activity of these channels are predicted to have therapeutic potential in treating CNS disorders. Members of the TREK family of K2P channels (TREK1 and TREK2) have been shown to play an active role in neuroprotection, depression and pain, whilst TRESK, with high expression in sensory neurons, has a role in nociception. Sipatrigine, a neuroprotective agent and a derivative of the anticonvulsant lamotrigine, is a known antagonist of TREK channels whilst lamotrigine is thought to primarily inhibit TRESK channels. A new compound, Cen-092-C, has also been developed which is structurally similar to lamotrigine. However, its effects on K2P channels are unknown. To understand the mechanism of channel inhibition by drugs, the structure of TREK2 was solved and was co-crystallised with norfluoxetine. This showed that fenestration sites were important in channel and current inhibition. Furthermore, TRESK docking studies showed that F145 and F352 function in a similar way to TREK2 fenestration site, as the bulky phenylalanine faces into the pore, and are thought to be important for compound binding. The aim of this study is to clarify to differences in the inhibitory effect of these compounds on the selected K2P channels and to investigate the mechanism by which these compounds inhibit the channels current. Methods: Wild-type (WT) and mutated human K2P channels were transiently expressed in tsA-201 cells. The currents were measured using whole-cell patch-clamp electrophysiology. Results: Sipatrigine was shown to inhibit both TREK1 and TREK2 current. Lamotrigine was also found to inhibit TREK1 and to a lesser extent TREK2. Cen-092-C was found to be less effective on TREK1 and TRESK current compared to sipatrigine, but similar to lamotrigine results. The sipatrigine inhibitory effect, but not lamotrigine, was reduced by mutations on the M4 region at the fenestration site of TREK1 and TREK2 (L286 and L320). This sensitivity is selective at this site as other mutations in the central cavity showed no change in sipatrigine inhibition. Interestingly, the gain-of-function mutation (TREK1 E306A) on the C terminus showed a reduced sipatrigine inhibition. The effect of sipatrigine on TREK2 showed an over-recovery of current following wash-off of the compound. The wash-off current increase was not seen if the N-terminus length is forced into intermediate and short isoform. Sipatrigine inhibition was significantly decreased when the N-terminus was truncated. Sipatrigine has been shown to strongly inhibit TRESK. Lamotrigine was seen to inhibit TRESK current, however significantly less effective compared to sipatrigine. Furthermore, lamotrigine did show state dependent inhibition when TRESK is in the fixed activated state. Cen-092-C was also found to inhibit TRESK to a similar degree to lamotrigine, however there was no state dependent inhibition on TRESK current. The effects of these antagonists on TRESK has been shown to be abolished by mutations on two sites at the central cavity (F145 and F352). Conclusion: Lamotrigine was found not to be TRESK selective, contrary to other studies. Sipatrigine and lamotrigine inhibition works through binding to the channel. The fenestration site in both TREK1 and TREK2 has been found to be an important binding site of sipatrigine, differing from lamotrigine. This suggests that the structurally similar compounds bind to different regions of the TREK channels. Furthermore, the over recovery of TREK2 current after sipatrigine wash off is believed to show the compound's biphasic effect, where the underlying enhancement of current is hidden by the action of inhibition. The N-terminus is therefore believed to be important in regulating sipatrigine action on TREK2. It remains unclear whether the TRESK potential binding sites (F1452 and F352) are important in compound binding as the inserted mutation is believed to shift the channel to constant active state. The newly developed compound Cen-092-C shows a significantly greater degree of inhibition of TRESK when compared to TREK1. Cen-092-C and lamotrigine inhibition of TRESK is not significantly different. Lamotrigine inhibition of TRESK current is state dependent whereas sipatrigine and Cen-092-C inhibition of TRESK current is shown as state independent. All of this together could lead to a better understanding of how neuroprotective agents effect TREK and TRESK channels and could contribute to the design of more efficient ligands.
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Pang, Daniel. "The role of TASK two-pore-domain potassium channels in general anaesthesia." Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/7070.

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TASK channels, members of the two-pore-domain potassium channel family, contribute towards the resting membrane potential and have been implicated in the mechanism of general anaesthesia. Previous work from our group with a TASK-3 channel knockout (T3KO) mouse showed a reduction in halothane sensitivity using a loss of righting reflex (LORR) assay, and absence of the theta brain oscillation induced in wild type (WT) mice by halothane anaesthesia. Two further strains of knockout mice, the TASK-1 knockout (T1KO) and the double knockout (DKO: TASK-1 and -3 channels), were compared with WT using the LORR assay, cortical electroencephalogram recording in response to halothane and during sleep. The mechanistic basis for the diminished theta oscillation in T3KO mice was investigated by recording in CA1 pyramidal cells of the hippocampus. The LORR assay revealed a decrease in halothane sensitivity in T1KO but not DKO compared with WT. The T1KO strain had a theta oscillation induced by exposure to halothane similar to that of WT mice, whereas that observed in the DKO was intermediate between WT and T3KO. T1KO differed from other strains in that the distribution of sleep and wake periods was uniform across the diurnal cycle. The resting membrane potential did not differ between strains during control or halothane exposure. During control there was no strain difference in action potential (AP). Halothane altered AP shape in WT but not the T3KO strain. WT had a greater ability to sustain AP firing than T3KO during halothane. These data show that T1KO mice have decreased anaesthetic sensitivity and altered sleep structure compared with WT, indicating a role for this channel in anaesthetic sensitivity and sleep. The similar resting membrane potential and lack of response to halothane in the T3KO makes pyramidal cells an unlikely source of the theta ablation observed.
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Lee, Mun Ching. "Regulation of voltage-gated potassium (Kv) and two-pore domain potassium (K2P) channels implicated in pulmonary hypertension." Thesis, University of Kent, 2018. https://kar.kent.ac.uk/67654/.

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Background: Kv2.1 and TASK-1 channels are two main contributors of K+ currents in pulmonary artery smooth muscle cells (PASMC). Dysregulation of these channels has been implicated in the pathogenesis of pulmonary hypertension (PH). This thesis aims to delve deeper into the implications of the regulation of Kv2.1 by Kv9.3 in PH. Another subject of interest would be whether NADPH oxidase type 4 (Nox4), one of the major reactive oxygen species (ROS) producers in the PASMC, modulates Kv2.1, Kv9.3, and TASK-1 channels. The effects of several redox agents are also investigated as potential modulators of Kv2.1, Kv9.3, and TASK-1. In addition, this thesis also examined the effect of a Kv2-channel blocker, stromatoxin, on Kv2.1 and Kv9.3. Finally, since amphoterin-induced gene and open reading frame (AMIGO) proteins have recently been shown as novel Kv2.1-interacting partners, their effects on Kv2.1 and/or Kv9.3 are also explored in this study. Experimental approach: Whole-cell patch clamp electrophysiology was used to measure currents of the ion channels expressed in modified tsA-201 cells, in the absence and presence of Nox4 AMIGO and other regulatory molecules. Immunohistochemistry was deployed to visualize the distribution of Kv2.1 and Kv9.3 proteins in the rat lungs and hearts. Key results and Conclusions: This study supports the findings that Kv9.3 regulates Kv2.1 by increasing the current amplitude, shifting the activation threshold to a more negative voltage range, and prolonging the slow component of time constant of deactivation. These effects could be beneficial in PH as this would mean cells could be brought back to its resting membrane potential faster and the transduction of the next action potential can be delayed. Kv2.1 and Kv9.3 have also been detected at the endothelium and PASMC in rat lungs and hearts, further substantiating the claim that these channels are potential players in regulating PH. AMIGO1 and AMIGO2 proteins are confirmed as regulators of Kv2.1 and Kv9.3 proteins. Nox4 does not regulate Kv2.1, Kv9.3, and TASK-1 channels expressed in tsA-201 cells. While hydrogen peroxide (H2O2) does not have any effect on Kv2.1 and Kv9.3, it abolished the current reduction effect of AMIGO2 on Kv2.1/Kv9.3. Other redox agents used in this study such as dithiothreitol (DTT), 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), and chloramine T (Ch-T) are not modulators of these channels expressed in tsA-201 cells. The lack of effect from Nox4 and these redox agents could suggest that the redox regulation of different Nox subunit/Kv channels combination varies for different cell types due to the different regulatory proteins present in different heterologous expression systems. As with the case of H2O2 and AMIGO2, it is likely that the regulatory proteins, which could facilitate the hypoxia-sensing properties of Nox4 and the effects of the redox agents on the ion channels, are missing in our heterologous expression system, compared with other host cells.
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Kennard, Louise Elizabeth. "Functional properties and regulation of the two-pore domain potassium channels TREK-1 and TASK-3." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497890.

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Book chapters on the topic "Tandem Pore Domain Potassium Channels"

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Zhang, Shaoying, and Huaiyu Yang. "Two-Pore Domain Potassium Channels in Pain and Depression." In Nonclassical Ion Channels in the Nervous System, 301–29. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9781003109266-17-17.

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Kemp, Paul J., Chris Peers, Paula Miller, and Anthony Lewis. "Oxygen Sensing by Human Recombinant Tandem-P Domain Potassium Channels." In Advances in Experimental Medicine and Biology, 201–8. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4419-9280-2_26.

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Plant, Leigh, and Steve Goldstein. "Two-Pore Domain Potassium Channels." In Handbook of Ion Channels, 261–74. CRC Press, 2015. http://dx.doi.org/10.1201/b18027-23.

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"Two-Pore Domain Potassium Channels." In Handbook of Ion Channels, 281–94. CRC Press, 2015. http://dx.doi.org/10.1201/b18027-27.

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Licher, Thomas. "Two-Pore Domain Potassium Channels." In xPharm: The Comprehensive Pharmacology Reference, 1–4. Elsevier, 2007. http://dx.doi.org/10.1016/b978-008055232-3.60433-7.

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Kamuene, Jordie M., Yu Xu, and Leigh D. Plant. "The Pharmacology of Two-Pore Domain Potassium Channels." In Handbook of Experimental Pharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg, 2021. http://dx.doi.org/10.1007/164_2021_462.

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Kim, Donghee. "Chapter 12 Two‐Pore Domain Potassium Channels in Sensory Transduction." In Current Topics in Membranes, 353–77. Elsevier, 2006. http://dx.doi.org/10.1016/s1063-5823(06)57011-5.

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Kasap, Merve, and Donard S. Dwyer. "Two-Pore Domain Potassium Channels (K2Ps) as Drug Targets in Neuroinflammation." In Neuroinflammation, 413–27. Elsevier, 2018. http://dx.doi.org/10.1016/b978-0-12-811709-5.00022-3.

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Thomas, D. "Two-Pore-Domain (K2P) Potassium Channels: Leak Conductance Regulators of Excitability☆." In Reference Module in Biomedical Sciences. Elsevier, 2014. http://dx.doi.org/10.1016/b978-0-12-801238-3.04797-8.

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Levitan, Irwin B., and Leonard K. Kaczmarek. "Ion Channels Are Membrane Proteins." In The Neuron, 85–102. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199773893.003.0005.

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Molecular structures of voltage-gated sodium and potassium channels both have 24 membrane-spanning segments, in addition to a domain that contributes to the channel pore. In sodium channels, this overall structure is achieved with a single primary subunit containing four homologous domains, each with six membrane-spanning segments. The primary subunit of potassium channels, however, is smaller and resembles one of the four homologous domains in the sodium channel; four of these primary subunits come together to form a functional potassium channel. Experiments have revealed channel protein regions involved in such functions as voltage-dependent activation, inactivation, and ion selectivity. Some functions of voltage-dependent channels do not involve global changes in protein conformation but can be assigned to discrete structural modules in the channel protein. Inferences from mutational analysis, particularly those related to channel gating, conduction, and selectivity, have been confirmed and extended by elucidating the three-dimensional structures of several voltage-dependent ion channels.
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Conference papers on the topic "Tandem Pore Domain Potassium Channels"

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Schwingshackl, Andreas, Alina Nico West, Patrudu S. Makena, Vijay K. Gorantla, Scott E. Sinclair, and Christopher M. Waters. "Hyperoxia And Mechanical Stretch Regulate Expression Of Two-pore-domain Potassium (K2P) Channels In Lung Epithelium." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6789.

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