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BioAssay record AID 623912 submitted by Johns Hopkins Ion Channel Center: SAR Analysis for the identification of inhibitors of the two-pore domain potassium channel KCNK9 - Selectivity assay against KCNK3: FluxOR Assay CRC 2.
BioAssay record AID 588761 submitted by Johns Hopkins Ion Channel Center: SAR Analysis for the identification of selective inhibitors of the two-pore domain potassium channel KCNK9 in KCNQ2 expressing cells: FluxOR Assay CRC.
Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a
Blockade of voltage-gated sodium (Na+) channels by local anesthetics represents the main mechanism for inhibition of impulse propagation. Local anesthetic-induced potassium (K+) channel inhibition is also known to influence transmission of sensory impulses and to potentiate inhibition. K+ channels involved in this mechanism may belong to the emerging family of background tandem pore domain K+ channels (2P K+ channels). To determine more precisely the effects of local anesthetics on members of this ion channel family, we heterologously expressed the 2P K+ channels TASK-2 (KCNK5), TASK-1 (KCNK3), and chimeric TASK-1/TASK-2 channels in oocytes of Xenopus laevis. TASK-2 cDNA-transfected HEK 293 cells were used for single-channel recordings. Local anesthetic inhibition of TASK-2 was dose-dependent, agent-specific, and stereoselective. The IC50 values for R-(+)-bupivacaine and S-(-)-bupivacaine were 17 and 43 μM and for R-(+)-ropivacaine and S-(-)-ropivacaine, 85 and 236 μM. Lidocaine (1 mM) inhibited TASK
Research shows that rats and humans on a high-fat diet (HFD) are less sensitive to satiety signals known to act via vagal afferent pathways. We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ganglia (NG) and decreased vagal response to satiety signals, which contribute to hyperphagia. We show that a 2-week HFD caused an upregulation of 2-pore domain TWIK-related spinal cord K+ (TRESK) and TWIK-related acid-sensitive K+ 1 (TASK1) channels by 330% ± 50% and 60% ± 20%, respectively, in NG. Patch-clamp studies of isolated NG neurons demonstrated a decrease in excitability. In vivo single-unit NG recordings showed that a 2-week HFD led to a 55% reduction in firing frequency in response to CCK-8 or leptin stimulation. NG electroporation with TRESK siRNA restored NG responsiveness to CCK-8 and leptin. Rats fed a 2-week HFD consumed ~40% more calories compared with controls. Silencing NG TRESK but not TASK1 channel expression ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Fig. 1 Reduction of functional TRESK channels in DRG neurons and its association with pain in bone lesion-bearing rats.. (A and B) TRESK immunofluorescence staining in ipsilateral L4/5 DRG neurons from naïve, phosphate-buffered saline (PBS)-injected, or bone-localized MRMT-1 tumor-bearing rats. Representative images (A) and a summary for the mean fluorescence intensity of TRESK immunostaining (B) are shown. n = 224 to 230 cells (from six rats) per time point per group. Two-way analysis of variance (ANOVA) followed by Bonferroni post hoc test: F3,1818 = 116.2, ***P , 0.001. (C and D) TRESK protein (C) and mRNA (D) abundance in the cells described in (A). n = 6 to 7 rats per time point per group. Two-way ANOVA followed by either Bonferroni post hoc test, F3,40 = 4.21 (C), or one-way ANOVA followed by Tukey post hoc test, F2,16 = 20.54 (D), ***P , 0.001. N, naïve; P, PBS; M, MRMT-1. (E and F) Representative TRESK current traces and a summary for the current density of both the total background ...
Introduction CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Methods Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1. Results K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA ...
Introduction CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Methods Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1. Results K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA ...
Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice. Adult C57BL/6 J wild-type (WT, N = 32) and TREK-1 KO (N = 33) mice were used in this study. The overall phenotype and bladder function were evaluated by gene and protein expression of TREK-1 channel, in vitro contractile experiments using detrusor strips in response to stretch and pharmacological stimuli, and cystometry in unanesthetized animals. TREK-1 KO animals had an elevated basal muscle tone
TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.. ...
Polyunsaturated fatty acid (PUFA)-activated two-pore domain potassium channels (K2P ) have been proposed to be expressed in the pulmonary vasculature. However, their physiological or pathophysiological roles are poorly defined. Here, we tested the hypothesis that PUFA-activated K2P are involved in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch clamp (PC) and myography. K2P -gene expression was examined in chronic hypoxic mice. qRT-PCR showed that the K2P 2.1 and K2P 6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P 2.1 and K2P 6.1 in the endothelium of pulmonary arteries and of K2P 6.1 in bronchial epithelium. PC showed pimozide-sensitive K2P -like K(+) -current activated by docosahexaenoic ...
TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute to the background conductance whose inhibition by angiotensin II stimulates aldosterone secretion. We used task1-/- mice to analyze the role of this channel in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism independent of salt intake, hypokalemia, and arterial low-renin hypertension. The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase was absent in the outer cortex normally corresponding to the zona glomerulosa, but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid homeostasis and zonation were independent of the sex in young mice, but were restricted to females in adults. Patch-clamp experiments on adrenal cells suggest that task3 and other K+ channels compensate for the task1 absence. ...
Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K(+) current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+) channel blockers was inhibited further by TASK inhibitors
Objective:To investigate the expression of two-pore domain potassium channel-TREK-1 on primary cultured neurons and astrocytes and the temporal changes of TREK-1 expression in astrocytes under hypoxia insult.Methods: The cortical neurons and astrocytes were cultured.The expression of TREK-1 in cultured neurons and astrocytes were analyzed by double immunofluorescence staining.The temporal changes of TREK-1 expression in astrocytes under hypoxia insults were detected by Real-time PCR.Results: The TREK-1 immuno-reactivity was expressed on both the neurons and astrocytes under normal condition.During hypoxia insult,the TREK-1 expression on astrocyte increases at early phases and decreases gradually at late phase.Conclusion: The TREK-1 immunoreactivity is expressed on both the neurons and astrocytes.In astrocytes under hypoxia,there are temporal changes on TREK-1 expression.
Two-pore domain K+ (K2P) channels generate K+ leak current, which serves a vital role in controlling and modulating neuronal excitability. This diverse family of K+ channels exhibit distinct expression and function across neuronal tissues. TWIK-related spinal cord K+ channel (TRESK) is a K2P channel with a particularly enriched role in sensory neurons and in vivo pain pathways. Here, we explored the role of TRESK across molecularly distinct sensory neuron populations and assessed its contribution to different sensory modalities. We found TRESK mRNA only in select populations of C- and A-δ nociceptors, in addition to low threshold D-hair afferents. Neurons from mice in which TRESK has been ablated demonstrated marked hyperexcitability, which was amplified under inflammatory challenge. Detailed behavioral phenotyping of TRESK knockout mice revealed specific deficits in somatosensory processing of noxious and non-noxious stimuli. These results demonstrate novel roles of TRESK in somatosensory processing
Potassium channels, found throughout the animal and plant kingdoms, play important roles in maintaining membrane potentials and regulating action potential firing, shape, and duration, among other functions. Using the Xenopus laevis (frog) oocyte as model system, we induced high expression of sodium and potassium voltage-gated channels and recorded action potentials by a modification of the two-electrode voltage-clamp recording technique. The voltage-dependent sodium conductance was due to expression of the skeletal muscle NaV channel (NaV1.4) and the delayed rectifier voltage-dependent potassium conductance was due to expression of a Shaker (Kv1) potassium channel. Upon this background, we mixed different potassium-selective ion channels, such as inwardly rectifying potassium (KIR) channels, tandem pore domain (K2P) potassium channels and voltage-gated (KV) channels. We analyzed how these potassium channels affected firing thresholds, reliability of action potential generation, action potential
in the normal resting state, the nerve has a negative membrane potential of -70 mv. this resting potential is determined by the concentration gradients of 2 major ions, na+ and k+, and the relative membrane permeability to these ions (also known as leak currents). the concentration gradients are maintained by the sodium/potassium atp pump (in an energy-dependent process) that transports sodium ions out of the cell and potassium ions into the cell. this active transport creates a concentration gradient that favors the extracellular diffusion of potassium ions. in addition, because the nerve membrane is permeable to potassium ions and impermeable to sodium ions, 95% of the ionic leak in excitable cells is caused by k+ ions in the form of an outward flux, accounting for the negative resting potential. the recently identified 2-pore domain potassium (k2p) channels are believed to be responsible for leak k+ currents ...
Outward rectifying potassium channel. Produces rapidly activating outward rectifier K(+) currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation (By similarity).
Outward rectifying potassium channel. Produces rapidly activating outward rectifier K(+) currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation.
Several recent ion channel structures have revealed large side portals, or fenestrations at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets can occupy the fenestrations and partially penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the
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Two-pore domain K(+) (K2P) channels play an important role tuning β-cell glucose-stimulated insulin secretion (GSIS). The K2P channel TALK-1 is linked to type-2 diabetes risk through a coding sequence polymorphism (rs1535500); however, its physiological function has remained elusive. Here, we show that TALK-1 channels are expressed in mouse and human β-cells, where they serve as key regulators of electrical excitability and GSIS. We find that the rs1535500 polymorphism, which results in an alanine to glutamate substitution in the C-terminus (Ct) of human TALK-1, increases channel activity. Genetic ablation of TALK-1 results in β-cell membrane potential (Vm) depolarization, increased islet Ca(2+) influx, and enhanced 2(nd) phase GSIS. Moreover, mice lacking TALK-1 channels are resistant to high-fat diet induced elevations in fasting glycemia. These findings reveal TALK-1 channels as important modulators of 2(nd) phase insulin secretion, and suggest a clinically relevant mechanism for ...
en] The acid-sensitive, two-pore domain K(+) channel, TASK-1, contributes to the background K(+) conductance and membrane potential (Em) of rat and human pulmonary artery (PA) smooth muscle cells (SMC), but its role in regulating tone remains elusive. This study aimed to clarify the role of TASK-1 by determining the functional properties of PA from mice in which the TASK-1 gene was deleted (TASK-1/3 KO), in comparison with wild type (WT) C57BL/6 controls. Small vessel wire myography was used to measure isometric tension developed by intact PA. Em and currents were recorded from freshly isolated PASMC using the perforated patch-clamp technique. Reverse-transcription polymerase chain reaction (RT-PCR) was used to estimate K(+) channel expression. We could find no difference between PA from WT and TASK-1/3 KO TASK KO mice. They showed similar constrictor responses to a range of agonists and K(+) concentrations, the K(+) channel blockers 4-aminopyridine, tetraethylammonuim ions and XE991. ...
A combined systematic alanine scanning and molecular modelling approach reveals the molecular basis for an allosteric inhibition mechanism of K+-flux gating in K2P channels.
Becker, D.; Geiger, D.; Dunkel, M.; Roller, A.; Bertl, A.; Latz, A.; Carpaneto, A.; Dietrich, P.; Roelfsema, M. R. G.; Voelker, C. et al.; Schmidt, D.; Mueller-Roeber, B.; Czempinski, K.; Hedrich, R.: AtTPK4, an Arabidopsis tandem-pore K+ channel, poised to control the pollen membrane voltage in a pH- and Ca2+-dependent manner. Proceedings of the National Academy of Sciences of the United States of America 101 (44), pp. 15621 - 15626 (2004 ...
Author(s): Zilberberg, N; Ilan, N; Goldstein, SA | Abstract: Essential to nerve and muscle function, little is known about how potassium leak channels operate. KCNKØ opens and closes in a kinase-dependent fashion. Here, the transition is shown to correspond to changes in the outer aspect of the ion conduction pore. Voltage-gated potassium (VGK) channels open and close via an internal gate; however, they also have an outer pore gate that produces C-type inactivation. While KCNKØ does not inactivate, KCNKØ and VGK channels respond in like manner to outer pore blockers, potassium, mutations, and chemical modifiers. Structural relatedness is confirmed: VGK residues that come close during C-type gating predict KCNKØ sites that crosslink (after mutation to cysteine) to yield channels controlled by reduction and oxidization. We conclude that similar outer pore gates mediate KCNKØ opening and closing and VGK channel C-type inactivation despite their divergent structures and physiological roles.
Kashmir Great Lakes Trek on of the fascinating trek in India and popular among trekkers, as Kashmir known as Heaven on Earth and trek through that region becomes more attractive and gives unforgettable experience of life. This trek of 8 days starts from sonmarg pass through beautiful meadows Kashmir, scenic lakes, waterfalls, water streams.. It´s simply magnificient. Of course you will get to see a lot of cultural highlights as well. One for sure is to meet some shepherds with their families and herds druing our trek. On your way from Srinagar to Sonamarg and as well on the houseboat you will get an idea of the local culture, food and religion in Kashmir. Everything is very colourful and you will get to see a lot of mosques and religous people on your way. Our other trek routes are Goechala Trek, Sandakphu-Phalut Trek, Rachela (Neora Valley) Trek, Phoktey Dara Trek, Uttarey Dzongri Round Singalila Trek, Varsey Phalut Trek, Tosar Lake Trek etc.. How to Reach. By Air :- Most major air carriers ...
Inwardly rectifying potassium channels (K(ir)), comprising four subunits each with two transmembrane domains, M1 and M2, regulate many important physiological processes. We employed a yeast genetic screen to identify functional channels from libraries of K(ir) 2.1 containing mutagenized M1 or M2 dom …
TASK-2 (KCNK5) two-pore domain, pH-sensitive, voltage-insensitive, outward rectifying K+ channel (K+ , Rb+ ,, Cs+ , NH4+ , Na+ ≈ Li+), present in renal epithelia. Regulated [inhibited] via group 1 metabolotropic glutamate receptors and by inositol phosphates (Chemin et al., 2003). TASK-2 gating is controlled by changes in both extra- and intracellular pH through separate sensors: arginine 224 and lysine 245, located at the extra- and intracellular ends of transmembrane domain 4, respectively. TASK-2 is inhibited by a direct effect of CO2 and is regulated by and interacts with G protein subunits. TASK-2 takes part in regulatory adjustments and is a mediator in the chemoreception process in neurons of the retrotrapezoid nucleus where its pHi sensitivity could be important in regulating excitability and therefore signalling of the O2/CO2 status. Extracellular pH increases, brought about by HCO3- efflux from proximal tubule epithelial cells may couple to TASK-2 activation to maintain ...
A list of events which occurred on the 8th of September. The date, September 8th, celebrates the original series premiere back in 1966. On September 8th, CBS All Access is holding an all-day streaming event to commemorate the 54th anniversary of the premiere of the original Star Trek television show. We are all citizens of the same universe, and at the end of the day thats all that matters. Deep Space Nine, Voyager, and Enterprise followed and then, in 2017, CBS All Access premiered Stark Trek: Discovery. The panel and discussions are free and offer longtime fans a way to celebrate the day and their favorite shows within the story of Star Trek. Ive cheated death. Page 2 of 3 < Prev 1 2 3 Next > Star Trek Day September 8th. 1966 TOS: The Man Trap airs as the Star Trek series premiere. DATE: September 8. Over the years, there have been multiple incarnations of Star Trek on TV and in movies. , Happy #StarTrekDay everyone pic.twitter.com/RkUgE7JZvd. After Star Trek: The Original Series ...
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Complete information for KCNK6 gene (Protein Coding), Potassium Two Pore Domain Channel Subfamily K Member 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Hemis to Stok Trek via Matho Phu - Trek No 05. Duration of Trek: 05 Days Best Time: Mid June to End of September Highest Point: Matho La (4820 m) Focus: Monasteries, Monks, People Villages Highlight: Remote villages, High mountain Passes Physical Challenge: Moderate overall
Yesterday we told you about DuroSports new retail outlet in Second Life. It was everything we expected a DuroSport store to be - which was exactly the problem. DuroSport has become so predictable that even their failures no longer surprise us. But there is a new development that even we find quite surprising. DuroSport has just announced an exclusive partnership with the most highly respected content franchise in history: Star Trek.. Yes, you read that correctly. Star Trek. Starting today, Star Trek and DuroSport Electronics have partnered to release what they are calling DeMastered episodes of Star Trek: The Original Series. The episodes are being made available exclusively through DuroSports new video download service called - predictably - DuroView.. We didnt mention this yesterday because, frankly, were expecting the Star Trek people might pull the plug on this deal at the last possible moment. From the second we heard about this deal, we kept telling them that they should opt-out of ...
Trek grading and walking times are average estimates only for people of average fitness and who are well acclimatised to the altitude. Some people will be much faster and others will find it more difficult and be much slower. Estimated times have been based on our experience with previous groups. Your own hiking speeds will depend on how well you have adjusted to the altitude as well as your own personal fitness level. The effects of altitude do make the hiking much harder than a similar trek closer to sea level would be and different people adjust to the altitude in a different timeframe.. You need to have average to good fitness and be able to hike a sustained uphill climb for up to 3 hours without distress and manage the long descents down from the passes to be able to enjoy these treks, and also be able to manage several nights sleeping in tents in sometimes very cold conditions.. We have graded most of the Huayhuash treks to be Hard. This not because of the technical difficulty of the treks ...
In the kidney, TWIK1 was localized in the brushborder and in subapical vesicles of the proximal tubule. Interestingly, expression and localization in the brushborder membrane of late proximal tubule (S3) were much stronger in female mice compared to males. Testosterone treatment of female mice led to reduced TWIK1 levels in the S3 segment suggesting a role of androgens in the regulation of TWIK1. In this nephron segment, TWIK1 colocalized with the sodium-dependent glucose transporter SGLT1. Similar to TWIK1, SGLT1 also showed sex-dependent expression and localization. We hypothesize that TWIK1 plays a role for the repolarization of the membrane voltage after depolarization of the luminal membrane by electrogenic transport systems, e.g. by Na+-coupled glucose transport. By this mechanism, TWIK1 would stabilize the driving force for voltage-dependent electrogenic substrate transport. In fact, TWIK1-/- mice exhibited a reduced maximal transport capacity for glucose ...
Day 01: Drive from Kathmandu to sole bazaar 650m via Betrawati approx. 7 hrs. Day 02: Trek from sole bazaar to Satdobate 1250m approx. 5 hrs. Day 03: Trek from Satdobate to Balche 1930m approx 5 hrs. Day 04: Trek from Balche to Gonga 2910m approx 7 hrs. Day 05: Trek from Gonga to Rupchet Kharka 3634m approx 5 hrs. Day 06: Trek from Rupchet Kharka to Mangchet Kharka via Singla Top approx 7hrs. Day 07: Trek from Mangchet Kharka to Pangsang Bhanjyang approx 7 hrs. Day 08: Trek and climb to Pangsang La Danda and trek back to Pangsang Bhanjyang approx 3 hrs. Day 09: Trek from Pangsang Bhanjyang to Chalise approx 7 hrs. Day 10: Trek from Chalise to Hindung approx 5 hrs. Day 11: Trek from Hindung to Rajgang Kharka approx 5 & ½ hrs. Day 12: Trek from Rajgang Kharka to Kalo Seto Kunda Black and White Lake)Ganesh Himal Base Camp approx 6 hrs. Day 13: Rest day at the Base Camp.. Day 14: Trek from Ganesh Himal Base Camp to Rajgang Kharka approx 6 hrs. Day 15: Trek from Rajgang Kharka to Chalise ...
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https://www.waylandgames.co.uk/star-trek-attack-wing/52580-star-trek-attack-wing-cardassian-galor-class 52580 Star Trek Attack Wing: Cardassian Galor Class https://www.waylandgames.co.uk/102938/star-trek-attack-wing-cardassian-galor-class.jpg 5.36 5.99 GBP InStock Home/Wargames & Miniatures/Wargames/Star Trek Attack Wing/ Home/Gift Ideas/ Star Trek Attack Wing is a tactical space combat HeroClix miniatures game, featuring ships from the Star Trek Universe. By using the FlightPath manoeuvre system, players engage in exploration and combat, traversing sprawling Star Trek space maps. Players have the ability to customise, upgrade, and assign famous crew-members to their fleets, which feature ships from the series prominent empires and forces as well as special stats and abilities, and unique manoeuvres on separate Heroclix Combat Dials.. Star Trek Deep Cuts Unpainted Miniatures, come with one highly-detailed ship. ...
Background Potassium is the major cation of intracellular fluid and an almost constant component of lean body tissues. A high intracellular concentration of potassium is maintained by the Na+/K+-ATPase pump. The movements of potassium out of cells and
Despite having multiple projects in the works, the Star Trek film franchises future is unclear. Its been almost four years since Star Trek Beyond opened in theaters. Though Paramount Pictures announced a sequel before Beyond hit theaters, the studio later scrapped those plans as actors exited the project. Franchise star Simon Pegg said in a recent interview that Star Trek might be better suited for television than for todays blockbuster-driven film market. His co-star, Zachary Quinto, is out promoting his latest television outing, the second season of NOS4A2. CominBook.com asked Quinto, who plays Spock in the Star Trek, what he thought of Peggs assessment of Star Treks future.. Its already thriving in the television format with Discovery and Picard and the spinoffs, Quinto said. I cant even keep track of how many new Star Trek stories are being told since our last film in 2016. All I know is that we, all of us, had an incredible experience making those films. If there is an appetite ...
Saru has been a standout character on Star Trek: Discovery, carrying on the tradition of the other as embodied by past Trek characters such as Mr. Spock, Data and Odo. Explorations of these characters and their histories are always welcome, making it a bit surprising the first visit to Kaminar was done in Short Treks. Due to the shorter format, it would be unfair to hold this episode to other character backstory-revealing episodes such as TOS Amok Time or TNG Datalore. However, The Brightest Star was still able to deliver quite a bit in terms of laying out the lore of the Kelpiens.. We already knew that they were prey to a predator species. We have seen Sarus flight instinct and ability to sense the coming of death exhibited during the first season of Discovery. Saru had talked about how the Kelpiens were hunted and one could have imagined something that evoked the alien hunters featured in The Predator franchise, or their Star Trek: Voyager knock-offs, the Hirogen. However, the writing ...
Star Trek Into Darkness, the second installment of the rebooted Star Trek series - depicting the early careers of Kirk, Spock and the whole Enterprise crew - has the self-consciousness of a sequel. The last film had an amazing opening sequence, showing the birth of Captain Kirk and the death of his father. [...] in Star Trek Into Darkness they try to top it, by beginning the movie with Kirk on the run from the primitive, makeup-wearing natives of a doomed planet. Yet every time Star Trek Into Darkness looks as though its about to retreat behind the wall of silly, something happens that surprises, or delights, or demonstrates the filmmakers genuine knowledge of and affection for these characters. An interplanetary terrorist organization, run by John Harrison - a mysterious and icy-cold superman (Benedict Cumberbatch), detonates a bomb at the Federations London archive. Star Trek Into Darkness is a straight-up summer action movie, and so its rather interesting and surprising to see how
J.J. Abrams is often dinged by Trekkers for daring to futz with the Star Trek universe (they'll probably stone him when he revives Star Wars). I thought his 2009 Trek reboot proved the naysayers nuts. And now Abrams boldly goes into Star Trek Into Darkness, and crushes it again. It's more fun and more intense, without giving less to the characters. The Enterprise crew is back, plus a sexy stowaway (Alice Eve). Zachary Quinto is a marvel as the Vulcan Spock, war between intellect and id raging inside his half-human brain. This brings tension into his bromance with Kirk (a fired-up Chris Pine), the rule-busting starship officer not averse to a three-way with two aliens.. Like the best of Trek on TV, the script, by Roberto Orci, Alex Kurtzman and the invaluable Damon Lindelof (Abrams' co-creator on Lost), is sharply topical. Domestic terrorism drives the plot, putting Kirk and Spock into conflict with a villain for the ages. He'd be John Harrison, and the brilliant Benedict ...
Trek Lamayuru to Alchi Trek offers a short trek in Ladakh with visits to Lamayuru and Alchi Monasteries. To enjoy the beauty of Ladakh and its monasteries visit now.
Pin Parvati Pass is the most glamorous Trans-Himalayan Trek in India. It is in the top five most coveted treks rated by experienced Trekkers. At the same time, the trek throws back quite a few challenges. Based on our experience, we have prepared an FAQ on 10 most asked questions about Pin Parvati Pass Trek.
Trek Madone SLR 6 Disc Speed 52 Voodoo Trek White/Blue - Madone SLR 6 D Speed 52 Voodoo Trek White/BlueDie mitgelieferte Speed Concept Mono Bar Extens
Trek Fuel EX 7 ML (29 wheel) Trek Black/Purple Lotus - Fuel EX 7 NX ML 29 Trek Black/Purple LotusEs ist ein großartiges Trailbike mit Teile-Upgrades
I remember in middle school and high school I was obsessed with Star Trek. I had seen all the episodes in reruns many times. I had read Blishs adaptations of them a few times. I read Fosters much longer adaptations of the animated series episodes (Blish put 5 hour-long TOS episodes into a book - they read almost like scripts. Foster put a book out for each of the half-hour animated episodes. I imagine he filled in a lot of backstory and detail). I had some of them in a sort of hybrid-comic-book form where it was pictures from show with talk bubbles. I read the first 90 or so Star Trek novels (before they started coming out too fast for my moneys). I read the technical manuals. I read the book by the writer of Trouble with Tribbles (David Gerold?) where he talked about how it was adapted into the episode and all the changes he had to make (not mentioned: changing anything about the use of credits to buy things on the station). I owned all the FASA Star Trek RPG supplements and tried to play ...
I remember in middle school and high school I was obsessed with Star Trek. I had seen all the episodes in reruns many times. I had read Blishs adaptations of them a few times. I read Fosters much longer adaptations of the animated series episodes (Blish put 5 hour-long TOS episodes into a book - they read almost like scripts. Foster put a book out for each of the half-hour animated episodes. I imagine he filled in a lot of backstory and detail). I had some of them in a sort of hybrid-comic-book form where it was pictures from show with talk bubbles. I read the first 90 or so Star Trek novels (before they started coming out too fast for my moneys). I read the technical manuals. I read the book by the writer of Trouble with Tribbles (David Gerold?) where he talked about how it was adapted into the episode and all the changes he had to make (not mentioned: changing anything about the use of credits to buy things on the station). I owned all the FASA Star Trek RPG supplements and tried to play ...
I was going to write something snarky here, but I cant. I just cant. If that trailer is any indication, Star Trek: Beyond is going to be a hot pile of shit like Into Darkness. Cant say that Im surprised. After all, Justin Lin is the same guy who directed four of the Fast & Furious movies and that trailer shows that he went at Beyond just like one of those movies. I make no secret about my dislike of the reboot and this only increases those feelings. This isnt Star Trek, plain and simple. This is Paramount trying to squeeze as much money out of the franchise as they can by reducing Trek to nothing more than an action movie franchise ...
A double-page spread about UBC Library Vault appears on pages 28 and 29 of the spring 2009 issue of UBCs Trek magazine. A Vault image also appears on the inside front cover.. You can view a PDF of Trek here:. http://www.alumni.ubc.ca/files/pdf/trekmagazine/trek23-spring2009.pdf. ...
‎Star Trek, one of the most iconic and influential global television franchises, returns to television 50 years after it first premiered with STAR TREK: DISCOVERY. STAR TREK: DISCOVERY will follow the voyages of Starfleet on their missions to discover new worlds and new lifeforms, and one Starfleet o…
‎Star Trek, one of the most iconic and influential global television franchises, returns to television 50 years after it first premiered with STAR TREK: DISCOVERY. STAR TREK: DISCOVERY will follow the voyages of Starfleet on their missions to discover new worlds and new lifeforms, and one Starfleet o…
Live long and prosper. And collect cool Star Trek stuff like this Star Trek The Wrath of Khan Spock Bobble Head. It is Spock as he was dressed in Star Trek II.
Trekking list is a guideline to help you pack for your adventure. Also understand that the items listed below will vary a little according to the season and the trek duration. Those items marked by an are provided by High Spirit Treks inclusive in the service. The weight limit for your luggage is 35/36 pounds or 17/18 KG. The luggage will be carried by our porter but we required carrying your day-pack (with your valuables or anything important) on your own. We also suggest that you pack only what is necessary for the Trek. Rest of the things you may can store with us or at the Hotel.. Important documents and items. ...
Andharban Trek is one of the most beautiful & fascinating monsoon trek, passing through dense forest & walking on the valley edges
Dengan kondisi trek yang kurang bersahabat, tidak ada pebalap yang mampu memperbaiki catatan waktunya di sesi latihan ketiga.. Hal itu berarti sepuluh pebalap teratas di catatan waktu kombinasi setelah FP2 berhak lolos langsung ke babak kualifikasi kedua (Q2), demikian laman resmi MotoGP.. Sementara Q1 akan diramaikan oleh sejumlah nama besar seperti duet tim Suzuki Alex Rins dan Joan Mir, bersama Bagnaia, Aleix Espargaro (Aprilia), dan Alex Marquez (LRC Honda) yang bakal memperebutkan dua tiket ke Q2.. Kondisi trek basah cukup menyulitkan para pebalap pagi ini seperti juara GP Spanyol Jack Miller (Ducati) yang tergelincir di Tikungan 6, juga Iker Lecuona (KTM) yang terjatuh di 15 menit terakhir.. Pemuncak catatan waktu Johann Zarco kembali tampil kompetitif di balapan kandangnya setelah finis P6 di trek basah.. Sedangkan pebalap Prancis lainnya, Fabio Quartararo, yang membalap untuk pertama kali setelah menjalani operasi arm pump, tak mampu menembus 15 besar, seperti halnya tiga pebalap Yamaha ...
Mego 14″ Mr Spock (Star Trek). Mr. Spock is the first of three 14″ Star Trek figures from Mego corp. This figure was announced in 2019 but was unfortunately canceled due to factory closure. The original prototype shown at Toyfair used the heads from the classic Mego Star Trek the Motion picture 12″ Spock but Mego has decided to blow up the classic 8″ Spock head for this line. Hey, why fix what isnt broken? ...
Ganesh Himal Trek Trekking in Ganesh Himal is known as non-tourist trekking area of Nepal in comparison to Annapurna, Langtang and Everest region. We are 14 Days,Ganesh Himal Trek offers you spectular view of nature, sunshine crystal view of Ganesh Himal as well as view of Budhi Gandaki and Bhote Koshi.
Buy TREK FX 2 DISC WOMEN S - 2018 | - Free UK Delivery available. Cyclescheme & Finance options available in-store Buy TREK FX 2 DISC WOMEN S - 2018 | - Free UK Delivery available. Cyclescheme & Finance options available in-store Buy TREK
Star Trek News - Paramount has just released a new Star Trek Into Darkness featurette that incorporates previously seen and new clips/interviews. Check it out now at StarTrek.com!
Star Trek News - StarTrek.com welcomes back guest blogger Dayton Ward. Today, in his latest Ten For Ward feature, Ward picks his 10 favorite Star Trek audionovels.
Sar pass trek is one of the favorite moderate trek for the true trekkers. Have a magical 6 day trip in Sar Pass. Book the affordable sar pass trek packages. Connect with us on +91 9318840504
Jomsom Muktinath Trek-12 day trek to Jomsom and Muktinath is a short and wonderful trekking known as lower Mustang trek in Nepal price, dates 2021/22/23/24.
For nearly 50 years, Star Trek has been one of the most dominant forces in pop culture. Treks history stretches beyond the shows themselves, because Gene Rodenberrys vision of the future has inspired generations and broken boundaries. Want to learn more before next years anniversary? Look no further.
Dayara Bugyal Trek is beauty of snow-capped mountains, sprawling meadows and a stretch of welcoming wildflower throughout the way look so beautiful.