• 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)
  • After overnight exposure, however, pentamidine reduced hERG currents and inhibited trafficking and maturation of hERG with IC 50 values of 5 to 8 μM similar to therapeutic concentrations. (aspetjournals.org)
  • We found that gintonin enhances I Ks channel currents in concentration- and voltage-dependent manners. (molcells.org)
  • These results show that gintonin-mediated enhancement of I Ks channel currents is achieved through binding of the [Ca 2+ ] i /CaM complex to the C terminus of KCNQ1 subunit. (molcells.org)
  • Although both ketamine and halothane inhibit potassium currents through the Kv2.1 channel, their mechanisms of action at this potential target may be different. (silverchair.com)
  • Previous studies have confirmed that artemisinin can prevent arrhythmia by inhibiting K + currents. (fortunepublish.com)
  • In addition, SP induced a significant reduction of the delayed rectifier K+ currents (I-k) in about 42% of the patched neurons, when these were evoked with depolarizing potential steps. (torvergata.it)
  • ML277 provides insights and a tool to investigate the gating mechanism of KCNQ1 channels, and our study reveals a new strategy for treating long QT syndrome by specifically enhancing the AO state of native I Ks currents. (elifesciences.org)
  • Nitroprusside inhibited L-type calcium currents, transient outward currents and transient inward current, but increased delayed rectified potassium currents. (biomedcentral.com)
  • 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)
  • CRT effects are related to alterations in genes and microRNAs (miRs) expression, which regulate cardiac processes involved in cardiac apoptosis, cardiac fibrosis, cardiac hypertrophy and angiogenesis, and membrane channel ionic currents. (hindawi.com)
  • We verified this by showing that EGL-2 currents are inhibited by imipramine. (jneurosci.org)
  • Mutant EGL-2( gf ) channels exhibited a negative shift in voltage dependence of activation, and both wild-type (WT) and mutant currents were blocked by imipramine. (jneurosci.org)
  • Antiarrhythmic drugs exert their effects on cardiac electrical impulse formation and propagation via their interaction with ionic channels or with membrane receptors and cellular pumps that subsequently influence ionic currents across the cell membrane. (mhmedical.com)
  • Cardiac ionic currents commonly targeted by antiarrhythmic drugs include inward sodium current ( I Na ), L-type calcium current ( I Ca,L ), and delayed rectifier outward potassium current ( I K ), which consists of two components-a rapidly activating component ( I Kr ) and a slowly activating component ( I Ks ). (mhmedical.com)
  • 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)
  • Sotalol prolongs repolarization by inhibiting IKr, thereby prolonging the QT interval. (acc.org)
  • 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)
  • It is categorized as a Vaughn-Williams Class IC agent based upon its properties of causes a strong degree of sodium channel blockage with slowing cardiac conduction and a minimal effect on ventricular repolarization. (encyclopedia.pub)
  • 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)
  • ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. (ersjournals.com)
  • Previous studies have shown that inhibition of multiple potassium channels, including inwardly rectifying potassium current ( I k1 ), transient outward potassium current ( I to ), and delayed outward rectifier potassium current ( I k ) with similar potency, as well as prolongation of action potential duration (APD), are the major mechanisms of the antiarrhythmic effects of artemisinin [5]. (fortunepublish.com)
  • Probucol, a cholesterol-lowering drug, induces LQTs by inhibiting the expression of the hERG channel. (current-pharmaceutical-design.com)
  • Results: In this study, we demonstrated that 1 μM matrine and oxymatrine could rescue the hERG current and hERG surface expression inhibited by probucol. (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)
  • 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)
  • However, gintonin had no effect on hERG K + channel activity. (molcells.org)
  • 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)
  • 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)
  • Moreover, we reveal that, in male and female rats, this action depends on M-like potassium conductance. (jneurosci.org)
  • 3. Stuhmer W, Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, and Pongs O (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. (aspetjournals.org)
  • IKr mediates the rapid component of the delayed rectifier potassium current. (acc.org)
  • Therefore, although current guidelines suggest that outpatient initiation of sotalol remains a reasonable approach in those without obvious risk factors and a baseline QT less than 450ms (6) , this case reflects the importance of continued vigilance due to delayed risk of proarrhythmia, particularly in women and those with renal dysfunction or bradycardia. (acc.org)
  • Docosahexaenoic acid (DHA) inhibited the sodium current with ultrafast kinetics. (csic.es)
  • 1 As one major target of volatile anesthetics in the heart, the L-type Ca 2+ channel, responsible for the L-type Ca 2+ current (I Ca,L ), has been identified. (asahq.org)
  • Halothane accelerated the time constant of current inactivation, whereas ketamine affected this parameter minimally in both channel types. (silverchair.com)
  • This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field. (ersjournals.com)
  • Quinidine also blocks the slowly inactivating, tetrodotoxin -sensitive Na current, the slow inward calcium current (I Ca ), the rapid (I Kr ) and slow (I Ks ) components of the delayed potassium rectifier current , the inward potassium rectifier current (I KI ), the ATP-sensitive potassium channel (I KATP ) and I to . (explained.today)
  • A previous study reported that artemisinin affected the amplitude of ionic current in intact nodose ganglion neurons of adult rats by blocking the voltage-gated Na + , K + , and N-type Ca 2+ channels?suggesting the probable mechanism of anti-arrhythmia [6]. (fortunepublish.com)
  • Recent research has shown the ability of artemisinin to attenuate the voltage-gated Na + ( I Na ) and delayed-rectifier K + current (I K(DR) ) in endocrine or neuroendocrine cells [7]. (fortunepublish.com)
  • Nifedipine was prepared at a concentration of 10 mM to inhibit the calcium current. (fortunepublish.com)
  • In the current study, we have evaluated the ability of substance P (SP) and other neurokinin I receptor (NK1) agonists to protect, in a dose-and time-dependent manner, primary cultures of rat cerebellar granule cells (CGCs) from serum and potassium deprivation-induced cell death (S-K5). (torvergata.it)
  • 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)
  • 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)
  • Potassium channel blockade and/or inward current enhancer. (mhmedical.com)
  • however, they Have also been shown to inhibit L-type Ca2+ current (ICa). (unideb.hu)
  • In myocytes paced at 1 Hz, neither diastolic [Ca2+](i) nor the amplitude of [Ca2+](i) transients was significantly altered by SEA0400 up to the concentration of 1 mu M, which was shown to inhibit the exchange current. (unideb.hu)
  • Using voltage-clamp techniques, the authors examined the effect of two general anesthetics (ketamine and halothane) on a rat brain potassium channel of known amino acid sequence, and further assessed whether the inhibition of the channel is altered by a partial deletion of the C-terminal sequence of this channel. (silverchair.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)
  • [12] [13] Inhibition of the Na v 1.5 channel is specifically involved in its antiarrhythmic effects as a class I antiarrhythmic agent. (explained.today)
  • Similar inhibition is observed with the mouse homolog MEAG, suggesting that inhibition of EAG-like channels may mediate some clinical side effects of this class of antidepressants. (jneurosci.org)
  • 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)
  • 2. Kamb A, Weir M, Rudy B, Varmus H, and Kenyon C (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. (aspetjournals.org)
  • 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)
  • Sotalol is a class III antiarrhythmic agent that blocks beta- adrenergic receptors and the IKr potassium channel. (acc.org)
  • Many researchers are pursuing the development of antagonists that block TLR receptors either by inhibiting activation of TLRs or signaling pathways downstream of TLRs 7 . (nature.com)
  • Artemisinin attenuates I Na by modulating the voltage dependence of the Na + channel similar to the class I anti-arrhythmia agents. (fortunepublish.com)
  • New insights into the mechanisms underlying AF have identified promising new approaches, including the modulation of atrium-specific ion channels, connexins and the ryanodine receptor, the prevention of remodelling processes that lead to the arrhythmia as well as specific molecular events involved in arrhythmia generation. (nature.com)
  • Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes. (unifesp.br)
  • suppressed delayed afterdepolarization in 4 (80%) of 5 PV cardiomyocytes. (biomedcentral.com)
  • Gintonin-mediated activation of the I Ks channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP 3 receptor antagonist, and the calcium chelator BAPTA. (molcells.org)
  • In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I Ks channel activity by expressing human I Ks channels in Xenopus oocytes. (molcells.org)
  • In the present study, we used the Xenopus oocyte gene expression system to investigate the molecular mechanisms underlying how gintonin-mediated [Ca 2+ ] i transients are coupled to the regulation of I Ks channel activity. (molcells.org)
  • Kuo, 1998 ), but the molecular identities of these channels are unknown. (jneurosci.org)
  • In HEK 293T cells transfected with an HIV-1 molecular clone, PACT unexpectedly inhibited PKR and eIF2 phosphorylation and increased HIV-1 protein expression and virion production in the presence of either endogenous PKR alone or overexpressed PKR. (healthandwellnesssource.org)
  • Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of the dietary supplements of omega3FA against dofetilide-induced proarrhythmia observed in this animal model. (csic.es)
  • From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (bvsalud.org)
  • Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)
  • Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)
  • Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)
  • 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)
  • 12. Kim E, Niethammer M, Rothschild A, Jan YN, and Sheng M (1995) Clustering of Shaker-type K + channels by interaction with a family of membrane-associated guanylate kinases. (aspetjournals.org)
  • My laboratory is interested in ion channels and the membrane mechanisms that regulate the activation and function of T lymphocytes. (uc.edu)
  • Ion channels, located on the membrane of T cells, are the effectors which link antigen recognition to T cell function and gene regulation by controlling calcium homeostasis. (uc.edu)
  • Upon membrane depolarization, the KCNQ1 potassium channel opens at the intermediate (IO) and activated (AO) states of the stepwise voltage-sensing domain (VSD) activation. (elifesciences.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)
  • We show that the Caenorhabditis elegans egl-2 gene encodes an eag K + channel and that a gain-of-function mutation in egl-2 blocks excitation in neurons and muscles by causing the channel to open at inappropriately negative voltages. (jneurosci.org)
  • Subunit stoichiometry associated with altered channel gating induced by hERG1 agonist RPR-260243. (ucsd.edu)
  • They accomplish this through a number of mechanisms involving automaticity or ion channel dynamics, which in turn affect the propagation of the myocardial electrical impulse via change in conduction velocity or refractory period. (medscape.com)
  • Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. (ersjournals.com)
  • Figure 1: General mechanisms of AF and role of ion channels for AF stabilization. (nature.com)
  • Sig1R-modulatory activity was first found for phenytoin, an anticonvulsant drug that primarily acts by blocking the voltage-gated sodium channels. (frontiersin.org)
  • Quinidine acts as a blocker of voltage-gated sodium channels. (explained.today)
  • 5. Chandy KG, Williams CB, Spencer RH, Aguilar BA, Ghanshani S, Tempel BL, and Gutman GA (1990) A family of three mouse potassium channel genes with intronless coding regions. (aspetjournals.org)
  • 11. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, and Pongs O (1994) Inactivation properties of voltage-gated K + channels altered by presence of β-subunit. (aspetjournals.org)
  • This occurs through a direct block by R(+)pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. (unifesp.br)
  • Use dependence of ketamine and halothane action was observed in both Kv2.1 and the mutant channel, attributable to augmentation of C-type inactivation. (silverchair.com)
  • The link between inactivation and high affinity block of hERG1 channels. (ucsd.edu)
  • Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K + channels. (ucsd.edu)
  • Gintonin-mediated activation of both the I Ks channel was also blocked by the calmodulin (CaM) blocker calmidazolium. (molcells.org)
  • Interestingly, the addition of IFN inhibited virus growth and induced PKR induction and activation. (healthandwellnesssource.org)
  • Channels formed from KCNQ proteins consist of homomeric tetramers or heteromeric tetramers containing KCNQ as the α-subunit, and each KCNQ subunit is composed of six α-helical transmembrane segments (S1-S6). (molcells.org)
  • 10. Scott VE, Rettig J, Parcej DN, Keen JN, Findlay JB, Pongs O, and Dolly JO (1994) Primary structure of a β subunit of α-dendrotoxin-sensitive K + channels from bovine brain. (aspetjournals.org)
  • 13. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, and Trimmer JS (1995) Association and colocalization of K + channel α-and β-subunit polypeptides in rat brain. (aspetjournals.org)
  • 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)
  • PD1 blockade enhances K+ channel activity, Ca2+ signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer. (uc.edu)
  • In addition, some clinically used drugs may act via K + channel blockade ( Sanguinetti and Jurkiewicz, 1990 ). (jneurosci.org)
  • Calcium channel blockade. (mhmedical.com)
  • Mutations in the KCNQ1 [Ca 2+ ] i /CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I Ks channel. (molcells.org)
  • Mutations in K + channel sequences can lead to a variety of clinical disorders exemplifying their physiological importance [ 3 ]. (ersjournals.com)
  • Mutations that activate K + channels can lower cellular excitability, whereas those that inhibit K + channels may increase excitability. (jneurosci.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 KCNQ family of channel proteins (also known as Kv7) form K + -selective, voltage-gated channels ( Hille, 2001 ) that are slowly activating delayed rectifier K + ( I Ks ) channels. (molcells.org)
  • The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I Ks channels. (molcells.org)
  • Although it is not clear whether anesthetics interact directly with the C-terminus, which is thought to reside intracellularly, this portion of the channel protein clearly influences the actions of both anesthetics. (silverchair.com)
  • Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered. (explained.today)
  • The comparison between different dsRBPs showed that ADAR1, TAR RNA Binding Protein (TRBP) and PACT inhibit PKR and eIF2 phosphorylation in HIV-infected cells, whereas Staufen1 did not. (healthandwellnesssource.org)
  • The slowly activating delayed rectifier K + ( I Ks ) channel is a cardiac K + channel composed of KCNQ1 and KCNE1 subunits. (molcells.org)
  • In the heart, KCNQ1 associates with KCNE1 subunits to form I Ks channels that regulate heart rhythm. (elifesciences.org)
  • miR-133 inhibits proliferation and promotes apoptosis by targeting LASP1 in lupus nephritis. (nih.gov)
  • MiR-133a-5p inhibits androgen receptor (AR)-induced proliferation in prostate cancer cells via targeting FUsed in Sarcoma (FUS) and AR. (nih.gov)
  • In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. (mdpi.com)
  • Recent evidence is in favor of direct interactions between volatile anesthetics and channel proteins as the underlying mechanism of general anesthesia. (silverchair.com)
  • KCNQ channel proteins also co-assemble with KCNE1-4 subunits ( McCrossan and Abbott, 2004 ). (molcells.org)
  • KCNE1 suppresses the IO state so that the I Ks channel opens only to the AO state. (elifesciences.org)
  • Predicted to enable delayed rectifier potassium channel activity. (mcw.edu)
  • TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. (ersjournals.com)
  • A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment. (uc.edu)
  • Surprisingly, in SP-treated CGCs caspase-3 activity was not inhibited, while the calpain-1 activity was moderately reduced. (torvergata.it)
  • The EC 50 for the I Ks channel was 0.05 ± 0.01 μg/ml. (molcells.org)
  • 1. McKinnon D (1989) Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. (aspetjournals.org)
  • our unpublished data), suggesting a specific interaction between tricyclics and EGL-2 channels. (jneurosci.org)
  • The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. (mdpi.com)
  • Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus. (uc.edu)
  • Kv1.3 Channels Mark Functionally Competent CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer. (uc.edu)
  • The C-terminus SH3-binding domain of Kv1.3 is required for the actin-mediated immobilization of the channel via cortactin. (uc.edu)
  • Because they also play a role in how your heart works, numerous drugs have been developed, some are more specific to one type of channel (Amlodipine for Cav1.3, Verapamil for Cav1.2). (epiphanyasd.com)
  • Actions of anesthetics on ion channels are usually studied in vitro at room temperature. (asahq.org)
  • There is increasing evidence that direct interactions between volatile anesthetics and channel proteins may result in general anesthesia. (silverchair.com)
  • 4. Yokoyama S, Imoto K, Kawamura T, Higashida H, Iwabe N, Miyata T, and Numa S (1989) Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells: primary structure and functional expression from cDNAs. (aspetjournals.org)
  • Thus, new therapeutic approaches are needed to effectively inhibit the hyperinflammation produced by the overwhelming cytokine response during bacterial infection without developing resistance to secondary infection in abdominal infections like peritonitis. (nature.com)