• Synthetic Cm39 inhibits the voltage-gated K+ channel hKV1.2 with high affinity (Kd = 65 nM). (bvsalud.org)
  • 12)Li G R, Wang HB, Qin GW, Jin MW, Tang Q , et al.Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs. (tjmu.edu.cn)
  • In particular, TBAJ-587 inhibits hERG channel minimally and attenuates inhibition of the cardiac potassium channel protein coded by the hERG, which is important for cardiac repolarization. (immune-system-research.com)
  • We conclude that almitrine inhibits selectively the Ca 2+ -dependent K + channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug. (aspetjournals.org)
  • Isoflurane inhibits conduction in activated potassium channels . (mdwiki.org)
  • Xiao GS, Zhang YH, Wu W , Sun HY, Wang Y, Li GR. Genistein and tyrphostin AG556 decrease human atrial ultra-rapidly activating delayed rectifier potassium current by inhibiting EGFR tyrosine kinase. (ucsd.edu)
  • Background: The human ether-a-go-go-related gene (hERG) potassium channel is the rapidly activating component of cardiac delayed rectifier potassium current (IKr), which is a crucial determinant of cardiac repolarization. (current-pharmaceutical-design.com)
  • C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT-inhibitory properties comparable to the parent molecule, resveratrol. (nih.gov)
  • New cardiac safety testing guidelines are being finalised, as part of the FDA's Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aim to remove the over-reliance on screening against the hERG channel by expanding the panel to include hNa v 1.5, hCa v 1.2, hK v 4.3/KChiP2.2, hKir2.1 and hK v 7.1/KCNE1 human cardiac ion channels. (metrionbiosciences.com)
  • A CHO cell line expressing the hERG channel and the published Milnes hERG kinetic protocol were optimised for the QPatch 48 to create a biophysically and pharmacologically validated 'dynamic' hERG assay. (metrionbiosciences.com)
  • A recent report on the use of PaDEL fingerprints in conjunction with a k -NN strategy aimed at the prediction of chronic toxicity [ 25 ] prompted us to apply this approach to hERG-channel blockers, a far more focused system. (springer.com)
  • It was envisaged that publicly available data on a series of hERG-channel blockers could function as a starting point for model construction, and a series of 1953 PubChem compounds could act as basis for validation. (springer.com)
  • Probucol, a cholesterol-lowering drug, induces LQTs by inhibiting the expression of the hERG channel. (current-pharmaceutical-design.com)
  • We also demonstrated that matrine and oxymatrine were able to upregulate Sp1 expression which may be one of the possible mechanisms by which matrine and oxymatrine rescued probucol-induced hERG channel deficiency. (current-pharmaceutical-design.com)
  • 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. (immune-system-research.com)
  • The human Ether-a-go-go-Related Gene (hERG) encodes one of the major repolarizing potassium channels in the heart (KV11.1). (phrmafoundation.org)
  • Severe variants in KV11.1 can predispose individuals to a fatal ventricular arrhythmia, torsades de pointes, so restoring the function of the channel has clinical importance. (phrmafoundation.org)
  • Previous reports estimate that ~90% of KV11.1 variants are trafficking deficient and studies showed that treatment with E4031, a KV11.1 specific inhibitor, restored the trafficking for some channel variants. (phrmafoundation.org)
  • There is possibility of transferring knowledge from KV11.1 trafficking to other ion channel disorders. (phrmafoundation.org)
  • The human ether-a-go-go related gene (hERG, KCNH2) encodes for a voltage dependent K + ion channel (Kv11.1). (springer.com)
  • Clancy and colleagues chose the hERG (human Ether-à-go-go-Related Gene) potassium channel in the heart as the drug target in the first step of their computational pipeline. (newswise.com)
  • Background: Human ether-à-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. (elsevierpure.com)
  • Wu W , Dong MQ, Wu XG, Sun HY, Tse HF, Lau CP, Li GR. Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase. (ucsd.edu)
  • The human ether-à-go-go related gene potassium channel is an obligatory anti-target for drug developing on account of its essential role in cardiac repolarization and its close association with arrhythmia. (itmedicalteam.pl)
  • The KCNH2 gene belongs to a large family of genes that provide instructions for making potassium channels. (medlineplus.gov)
  • Channels made with KCNH2 proteins (also known as hERG1) are active in heart (cardiac) muscle. (medlineplus.gov)
  • The proteins produced from the KCNH2 gene and another gene, KCNE2 , interact to form a functional potassium channel. (medlineplus.gov)
  • Four alpha subunits, each produced from the KCNH2 gene, form the structure of each channel. (medlineplus.gov)
  • The genetic changes alter the function of ion channels made with the KCNH2 protein, increasing the channels' activity. (medlineplus.gov)
  • Sphingosine 1-phosphate (S1P) receptors and human ether-a 0 -go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. (scite.ai)
  • The ion channels affected include those responsible for the inward sodium or calcium currents and those responsible for the outward potassium current. (merckmanuals.com)
  • Zhang YH, Wu W , Sun HY, Deng XL, Cheng LC, Li X, Tse HF, Lau CP, Li GR. Modulation of human cardiac transient outward potassium current by EGFR tyrosine kinase and Src-family kinases. (ucsd.edu)
  • Candidate targets for anti-AF drugs include a potassium channel K(v)1.5, and the ionic currents I(KACh) and late I(Na), along with increased oxidative stress and activation of NFAT-mediated gene transcription. (nih.gov)
  • Up to now, it has been thought that therapeutic compounds causing QT prolongation are associated with direct block of the cardiac potassium channel human ether a-go-go-related gene (hERG), which encodes the α subunit of cardiac I Kr currents. (aspetjournals.org)
  • This effect of almitrine on the Ca 2+ -dependent component of K + currents was investigated further at the single-channel level in excised patches in the inside-out configuration. (aspetjournals.org)
  • These channels, which transport positively charged atoms (ions) of potassium out of cells, play key roles in a cell's ability to generate and transmit electrical signals. (medlineplus.gov)
  • As a result, the channels cannot properly regulate the flow of potassium ions in cardiac muscle cells. (medlineplus.gov)
  • As a result, more potassium ions flow out of cardiac muscle cells at a critical time during the heartbeat, which can lead to an irregular heart rhythm. (medlineplus.gov)
  • KCNQ proteins typically repolarise the plasma membrane of a cell after depolarisation by allowing the export of potassium ions, and are therefore involved in wide-ranging biological functions including cardiac action potentials ( 2 ), neural excitability ( 3 ), and ionic homeostasis in the gastrointestinal tract ( 4 ). (life-science-alliance.org)
  • The link between inactivation and high affinity block of hERG1 channels. (ucsd.edu)
  • Subunit stoichiometry associated with altered channel gating induced by hERG1 agonist RPR-260243. (ucsd.edu)
  • Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K + channels. (ucsd.edu)
  • Stoichiometry of altered hERG1 channel gating by small molecule activators. (ucsd.edu)
  • One beta subunit, produced from the KCNE2 gene, attaches (binds) to the channel and regulates its activity. (medlineplus.gov)
  • 7) Zheng YM , Park SW , Stokes L , Tang Q , Xiao JH , Wang YX 。Distinct activity of BK channel β1 subunit in cerebral and pulmonary artery smooth muscle cells. (tjmu.edu.cn)
  • Of these, 109 sequences showed identity to toxins that act on ion channels, 47 enzymes, 17 protease inhibitors (PINs), 11 defense peptides (HDPs), and 60 in other components. (bvsalud.org)
  • We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. (life-science-alliance.org)
  • These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors. (life-science-alliance.org)
  • Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K+ current in human atrial myocytes. (tjmu.edu.cn)
  • Moreover, we reveal that, in male and female rats, this action depends on M-like potassium conductance. (jneurosci.org)
  • Wu W , Sun HY, Deng XL, Li GR. EGFR Tyrosine kinase regulates small conductance Ca 2+ -activated K + (hSKCa1) channels expressed in HEK 293 cells. (ucsd.edu)
  • An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells. (epfl.ch)
  • In this preparation, almitrine inhibited the activity of a high-conductance (152 ± 13 pS), Ca 2+ -dependent K + channel by decreasing its open probability. (aspetjournals.org)
  • The specific function of a potassium channel depends on its protein components and its location in the body. (medlineplus.gov)
  • These changes prevent the protein from assembling into ion channels or alter the channels' structure or function. (medlineplus.gov)
  • The transient receptor potential melastatin 4 (TRPM4) protein is an intracellular Ca 2+ -activated non-selective cation channel, which is impermeable to Ca 2+ . (frontiersin.org)
  • Especially, the potassium channel K V 10.1 (Ether-á-go-go) is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins. (biomedcentral.com)
  • Zhang DY, Wu W , Deng XL, Lau CP, Li GR. Genistein and tyrphostin AG556 inhibit inwardly-rectifying Kir2.1 channels expressed in HEK 293 cells via protein tyrosine kinase inhibition. (ucsd.edu)
  • Ether-a-go-go-1 (Eag1) is a CNS-localized voltage-gated potassium channel that is found ectopically expressed in a majority of extracranial solid tumors. (mpg.de)
  • While circumstantial evidence linking Eag1 to tumor biology has been well established, the mechanisms by which the channel contributes to tumor progression remain elusive. (mpg.de)
  • A mutation that eliminates ion permeation fails to completely abolish xenograft tumor formation by transfected cells, indicating that Eag1 contributes to tumor progression independently of its primary function as an ion channel. (mpg.de)
  • The punctate localization of rat Eag1 K+ channels is conferred by the proximal post-CNBHD region. (epfl.ch)
  • Eag1, Eag2, and SK3 potassium channel expression in the rat hippocampus after global transient brain ischemia. (epfl.ch)
  • Differential localization of rat Eag1 and Eag2 potassium channels in the retina. (epfl.ch)
  • Differential localization of rat Eag1 and Eag2 K+ channels in hippocampal neurons. (epfl.ch)
  • A series of 172 molecular structures that block the hERG K + channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k -nearest neighbor model development. (springer.com)
  • Wu HJ, Sun HY, Wu W , Zhang YH, Qin GW, Li GR. Properties and molecular determinants of the natural flavone acacetin for blocking hKv4.3 channels. (ucsd.edu)
  • Molecular basis of potassium channels in pancreatic duct epithelial cells. (epfl.ch)
  • Three-dimensional structure of human Kv10.2 ion channel studied by single particle electron microscopy and molecular modeling]. (epfl.ch)
  • Molecular regions responsible for differences in activation between heag channels. (epfl.ch)
  • Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. (antikoerper-online.de)
  • We conclude that pentamidine prolongs the cardiac action potential by block of hERG trafficking and reduction of the number of functional hERG channels at the cell surface. (aspetjournals.org)
  • Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory. (epfl.ch)
  • In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. (lookformedical.com)
  • We made whole-cell patch-clamp recordings of recombinant ion channels, human atrial I(Kur), rat atrial I(KACh), cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. (nih.gov)
  • Transient receptor potential melastatin member 4 (TRPM4), a non-selective cation channel, mediates cell membrane depolarization in immune response, insulin secretion, neurological disorders, and cancer. (frontiersin.org)
  • Wu W , Wang Y, Deng XL, Sun HY, Li GR. Cholesterol down-regulates BK channels stably expressed in HEK 293 cells. (ucsd.edu)
  • The saxitoxins act by blocking sodium ion movement through voltage-dependent sodium channels in nerve and muscle cell membranes. (medscape.com)
  • RUZURGI is a potassium channel blocker indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age. (nih.gov)
  • 11) Tang Q, Li ZQ, Li W, et al.The 5-HT(2) antagonist ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels.Br J Pharmacol. (tjmu.edu.cn)
  • 8)Dong MQ, Sun HY, Tang Q , Tse HF , Lau CP, Li GR . Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase. (tjmu.edu.cn)
  • Based on amino acid sequence alignment with different K+ channel inhibitor scorpion toxin (KTx) families and phylogenetic analysis, Cm39 belongs to the α-KTx 4 family and was registered with the systematic number of α-KTx 4.8. (bvsalud.org)
  • Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. (life-science-alliance.org)
  • 13) Tang Q, Jin MW , Xiang JZ , Dong MQ , Sun HY , Lau CP , L i GR. The membrane permeable calciumchelator BAPTA-AMdirectly blocks human ether a-go-gorelatedgene potassium channels stably expressed in HEK 293 cells.Biochemical Pharmacology2007,74(11):1596-1607. (tjmu.edu.cn)
  • Pathogenic variants of the channel are responsible for causing long QT syndrome subtype 2 (LQT2), a disorder that prolongs ventricular contraction and action potential duration. (phrmafoundation.org)
  • C1 inhibited I(KACh)(IC₅₀ of 1.9 μmol·L(-1)) and the Na(v)1.5 sodium channel current (IC₅₀s of 3 and 1 μmol·L(-1) for peak and late components respectively). (nih.gov)
  • This study provides novel features of this current in ICC in physiological solutions and seeks to identify the channel isoform. (elsevierpure.com)
  • An additional CiPA channel component required for accurately predicting proarrhythmic liability is the 'late' or persistent sodium current. (metrionbiosciences.com)
  • Inhibitory effects of hesperetin on Nav1.5 channels stably expressed in HEK 293 cells and on the voltage-gated cardiac sodium current in human atrial myocytes. (tjmu.edu.cn)
  • Brevetoxins are polycyclic ethers that, like ciguatoxin , bind to and stimulate sodium flux through voltage-gated sodium channels in nerve and muscle. (medscape.com)
  • In situ hybridization and Kit immunohistochemistry were combined to assess ether-a-go-go-related gene (ERG) mRNA expression in ICC in mouse jejunum, while the translated message was assessed by immunofluorescence colocalization of ERG and Kit proteins. (elsevierpure.com)
  • EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. (epfl.ch)
  • Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. (epfl.ch)
  • External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor. (epfl.ch)
  • Roles of surface residues of intracellular domains of heag potassium channels. (epfl.ch)
  • Short QT Interval Syndromes The short QT interval syndromes (SQTS) are extremely rare congenital or very rarely acquired disorders of cardiac ion channel function or regulation that shorten ventricular myocyte action potential. (merckmanuals.com)
  • A sustained increase in the intracellular Ca²⁺ concentration induces proteolytic cleavage of EAG2 channel. (epfl.ch)
  • As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways. (nih.gov)
  • Three of them, p.A101T, p.S1044C and a double variant p.A101T/P1204L, led to a decreased expression and function of the channel. (frontiersin.org)
  • However, the physiological role for this channel in cardiac function remains unclear. (frontiersin.org)
  • Channelopathies are a group of genetic, autoimmune, or inflammatory conditions that alter cardiomyocyte ion channel function in a manner that predisposes to bradyarrhythmias or tachyarrhythmias in the absence of a structural heart disorder. (merckmanuals.com)
  • Either gain of function or loss of function in these ion channels, particularly when the abnormal channels are unevenly distributed, fosters abnormal electrophysiological environments. (merckmanuals.com)
  • and inflammatory disorders producing cytokinins that affect cardiomyocyte ion channel function are increasingly being recognized. (merckmanuals.com)
  • 6)Chen WANG, Yu-fang CHEN, Xiao-Qing QUAN,Huan WANG, Rui ZHANG, Jun-hua XIAO, Jia-ling WANG, Cun-Tai ZHANG,Ji-zhou XIANG, Qiang TANG .Effects of neferine on Kv4.3 potassium channelsand rabbit cardiac electrophysiology. (tjmu.edu.cn)
  • In particular, O 2 -sensitive K + channels seem to be different between rabbit and rat chemoreceptor cells. (aspetjournals.org)
  • CHO cells expressing the human ether-a-go-go related potassium channel (hERG, K v 11.1) were obtained from B'SYS. (metrionbiosciences.com)
  • Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types. (epfl.ch)
  • Inhibitory effects of neferine on Nav1.5 channels expressed in HEK293 cells. (tjmu.edu.cn)
  • The inhibitory effect of almitrine on Ca 2+ -dependent K + channels also was observed in GH3 cells. (aspetjournals.org)
  • Background:The identity of calcium channels in the thyroid is undefined. (scite.ai)
  • Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. (lookformedical.com)
  • Blocking of this channel has been associated with potential severe heart arrhythmia, and because of this, several drugs have been withdrawn from the market [ 1 - 6 ]. (springer.com)
  • Je pense que justement, le football américain devrait jouer un rôle plus important en Allemagne. (guido-conrad.de)
  • Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state. (epfl.ch)
  • In this study, Hamish S.Sutherland, et al presented compounds demonstrate more potent in vitro and in vivo anti-tubercular activity, with greatly attenuated human Ether-a-go-go Related Gene (hERG) blockade. (immune-system-research.com)
  • [3] Serious side effects can include malignant hyperthermia or high blood potassium . (mdwiki.org)