Celecoxib blocks cardiac Kv1.5, Kv4.3 and Kv7.1 (KCNQ1) channels: effects on cardiac action potentials.

Abstract:

:Celecoxib is a COX-2 inhibitor that has been related to an increased cardiovascular risk and that exerts several actions on different targets. The aim of this study was to analyze the effects of this drug on human cardiac voltage-gated potassium channels (Kv) involved on cardiac repolarization Kv1.5 (I(Kur)), Kv4.3+KChIP2 (I(to1)) and Kv7.1+KCNE1 (I(Ks)) and to compare with another COX-2 inhibitor, rofecoxib. Currents were recorded in transfected mammalian cells by whole-cell patch-clamp. Celecoxib blocked all the Kv channels analyzed and rofecoxib was always less potent, except on Kv4.3+KChIP2 channels. Kv1.5 block increased in the voltage range of channel activation, decreasing at potentials positive to 0 mV. The drug modified the activation curve of the channels that became biphasic. Block was frequency-dependent, increasing at fastest frequencies. Celecoxib effects were not altered by TEA(out) in R487Y mutant Kv1.5 channels but the kinetics of block were slower and the degree of block was smaller with TEA(in), indicating that celecoxib acts from the cytosolic side. We confirmed the blocking properties of celecoxib on native Kv currents from rat vascular cells, where Kv1.5 are the main contributors (IC(50)≈ 7 μM). Finally, we demonstrate that celecoxib prolongs the action potential duration in mouse cardiac myocytes and shortens it in guinea pig cardiac myocytes, suggesting that Kv block induced by celecoxib may be of clinical relevance.

journal_name

J Mol Cell Cardiol

authors

Macías A,Moreno C,Moral-Sanz J,Cogolludo A,David M,Alemanni M,Pérez-Vizcaíno F,Zaza A,Valenzuela C,González T

doi

10.1016/j.yjmcc.2010.09.012

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

984-92

issue

6

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(10)00343-3

journal_volume

49

pub_type

杂志文章
  • Skeletal muscle stem cells propagated as myospheres display electrophysiological properties modulated by culture conditions.

    abstract::In cardiac regenerative therapy, transplantation of stem cells to form new myocardium is limited by their inability to integrate into host myocardium and conduct cardiac electrical activity. It is now hypothesized that refining cell sorting could upgrade the therapeutic result. Here we characterized a subpopulation of...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.10.011

    authors: Poulet C,Wettwer E,Christ T,Ravens U

    更新日期:2011-02-01 00:00:00

  • Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats.

    abstract::We have previously reported that resistin induces hypertrophy and impairs contractility in isolated rat cardiomyocytes. To examine the long-term cardiovascular effects of resistin, we induced in vivo overexpression of resistin using adeno-associated virus serotype 9 injected by tail vein in rats and compared to contro...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2011.04.006

    authors: Chemaly ER,Hadri L,Zhang S,Kim M,Kohlbrenner E,Sheng J,Liang L,Chen J,K-Raman P,Hajjar RJ,Lebeche D

    更新日期:2011-08-01 00:00:00

  • Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling.

    abstract::Forces associated with blood flow are crucial not only for blood vessel development but also for regulation of vascular pathology. Although there have been many studies characterizing the responses to mechanical stimuli, molecular mechanisms linking biological responses to mechanical forces remain unclear. Hic-5 (hydr...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.09.024

    authors: Kim-Kaneyama JR,Takeda N,Sasai A,Miyazaki A,Sata M,Hirabayashi T,Shibanuma M,Yamada G,Nose K

    更新日期:2011-01-01 00:00:00

  • Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility.

    abstract::Multiple studies have shown that phospholamban (PLN) plays a key role in regulation of frequency-dependent increase of cardiac contraction, a hallmark of the contractile reserve in myocardium. However, the mechanisms underlying this relationship remain elusive. Phosphorylation of PLN occurs on residues: serine-16 (Ser...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2004.05.013

    authors: Zhao W,Uehara Y,Chu G,Song Q,Qian J,Young K,Kranias EG

    更新日期:2004-08-01 00:00:00

  • Atomic force and electron microscopic-based study of sarcolemmal surface of living cardiomyocytes unveils unexpected mitochondrial shift in heart failure.

    abstract::Loss of T-tubules (TT), sarcolemmal invaginations of cardiomyocytes (CMs), was recently identified as a general heart failure (HF) hallmark. However, whether TT per se or the overall sarcolemma is altered during HF process is still unknown. In this study, we directly examined sarcolemmal surface topography and physica...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2014.05.006

    authors: Dague E,Genet G,Lachaize V,Guilbeau-Frugier C,Fauconnier J,Mias C,Payré B,Chopinet L,Alsteens D,Kasas S,Severac C,Thireau J,Heymes C,Honton B,Lacampagne A,Pathak A,Sénard JM,Galés C

    更新日期:2014-09-01 00:00:00

  • Characterization of thromboxane A2/prostaglandin H2 binding sites in guinea pig cardiac membrane preparations.

    abstract::Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) induce platelet aggregation and are potent vasoconstrictors, and they have been implicated in coronary vasospasm and myocardial infarction. The TXA2 mimetic [1S-(1 alpha, 2 beta (5Z), 3 alpha (1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1109

    authors: Bowling N,Dubé GP,Kurtz WL,Brune KA,Saussy DL Jr,Dorn GW 2nd,Mais DE

    更新日期:1994-07-01 00:00:00

  • Impaired insulin signaling accelerates cardiac mitochondrial dysfunction after myocardial infarction.

    abstract::Diabetes increases mortality and accelerates left ventricular (LV) dysfunction following myocardial infarction (MI). This study sought to determine the impact of impaired myocardial insulin signaling, in the absence of diabetes, on the development of LV dysfunction following MI. Mice with cardiomyocyte-restricted knoc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.02.014

    authors: Sena S,Hu P,Zhang D,Wang X,Wayment B,Olsen C,Avelar E,Abel ED,Litwin SE

    更新日期:2009-06-01 00:00:00

  • Chemokine expression in myocardial ischemia: MIP-2 dependent MCP-1 expression protects cardiomyocytes from cell death.

    abstract::Chemokines are small molecular weight proteins that play important roles in inflammation. Originally described as chemotactic cytokines, chemokines stimulate the influx of leukocytes into specific tissue compartments. These molecules also modulate gene expression in both infiltrating and resident cells to mediate a va...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1503

    authors: Tarzami ST,Cheng R,Miao W,Kitsis RN,Berman JW

    更新日期:2002-02-01 00:00:00

  • The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis.

    abstract::Inflammation is critical in the pathobiology of atherosclerosis. An essential player in the inflammatory process in atherosclerosis are macrophages that scavenge oxidatively modified low-density lipoproteins (OxLDL) deposited in the subendothelium of systemic arteries that secrete a myriad of pro-inflammatory mediator...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2018.11.006

    authors: Chandra D,Londino J,Alexander S,Bednash JS,Zhang Y,Friedlander RM,Daskivich G,Carlisle DL,Lariviere WR,Nakassa ACI,Ross M,St Croix C,Nyunoya T,Sciurba F,Chen B,Mallampalli RK

    更新日期:2019-01-01 00:00:00

  • Phospholipid reorganization and bilayer destabilization during myocardial ischemia and reperfusion: a hypothesis.

    abstract::The ultrastructure of myocardial tissue was studied during ischemia and reperfusion and during reperfusion with a calcium-containing solution after a short period of calcium-free perfusion (calcium paradox). After ischemia an aggregation of the sarcolemmal intramembranous particles was observed. Subsequent reperfusion...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(88)90335-5

    authors: Post JA,Ruigrok TJ,Verkleij AJ

    更新日期:1988-03-01 00:00:00

  • Mechanisms of metabolic coronary flow regulation.

    abstract::Coronary blood flow is tightly adjusted to the oxygen requirements of the myocardium. The underlying control mechanisms keep coronary venous pO(2) at a rather constant level around 20mm Hg under a variety of physiological conditions. Because coronary flow may increase more than 5-fold during exercise without any signs...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2011.10.001

    authors: Deussen A,Ohanyan V,Jannasch A,Yin L,Chilian W

    更新日期:2012-04-01 00:00:00

  • Regulation of sodium-calcium exchange and mitochondrial energetics by Bcl-2 in the heart of transgenic mice.

    abstract::Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1476

    authors: Zhu L,Yu Y,Chua BH,Ho YS,Kuo TH

    更新日期:2001-12-01 00:00:00

  • Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation.

    abstract::This study was undertaken to evaluate the direct cardioprotective effect of trimetazidine (TMZ), an anti-anginal drug devoid of haemodynamic action, on isolated myocytes. Cultured rat ventricular myocytes were treated with the drug 16 h and 1 h before the experiments. The drug-treated cells and control cells were plac...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1994.1116

    authors: Fantini E,Demaison L,Sentex E,Grynberg A,Athias P

    更新日期:1994-08-01 00:00:00

  • Connexin40 abnormalities and atrial fibrillation in the human heart.

    abstract::Normal atrial conduction requires similar abundances and homogeneous/overlapping distributions of two connexins (Cx40 and Cx43). The remodeling of myocyte connections and altered electrical conduction associated with atrial fibrillation (AF) likely involves perturbations of these connexins. We conducted a comprehensiv...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2014.08.021

    authors: Gemel J,Levy AE,Simon AR,Bennett KB,Ai X,Akhter S,Beyer EC

    更新日期:2014-11-01 00:00:00

  • Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761).

    abstract::Hemodynamic and electron spin resonance analyses were used to assess the in vivo and in vitro cardioprotective and antioxidant effects of therapeutically relevant doses of Ginkgo biloba extract (EGb 761) and its terpenoid constituents (ginkgolides A and B, bilobalide) in the rat. Significant anti-ischemic effects, ind...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0316

    authors: Pietri S,Maurelli E,Drieu K,Culcasi M

    更新日期:1997-02-01 00:00:00

  • Impaired cell shortening and relengthening with increased pacing frequency are intrinsic to the senescent mouse cardiomyocyte.

    abstract::Increased heart rate enhances cardiac contractility and accelerates relaxation. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be impaired in senescent myocardium. While senescent myocardium is characterized by decreased sarc...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2000.1239

    authors: Lim CC,Apstein CS,Colucci WS,Liao R

    更新日期:2000-11-01 00:00:00

  • Loss of myocardial retinoic acid receptor α induces diastolic dysfunction by promoting intracellular oxidative stress and calcium mishandling in adult mice.

    abstract::Retinoic acid receptor (RAR) has been implicated in pathological stimuli-induced cardiac remodeling. To determine whether the impairment of RARα signaling directly contributes to the development of heart dysfunction and the involved mechanisms, tamoxifen-induced myocardial specific RARα deletion (RARαKO) mice were uti...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2016.08.009

    authors: Zhu S,Guleria RS,Thomas CM,Roth A,Gerilechaogetu F,Kumar R,Dostal DE,Baker KM,Pan J

    更新日期:2016-10-01 00:00:00

  • Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha.

    abstract::Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (DeltaG approximately (ATP)), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice ov...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.10.029

    authors: Shen W,Vatner DE,Vatner SF,Ingwall JS

    更新日期:2010-04-01 00:00:00

  • Role of CaMKII in post acidosis arrhythmias: a simulation study using a human myocyte model.

    abstract::Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increas...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2013.04.018

    authors: Lascano EC,Said M,Vittone L,Mattiazzi A,Mundiña-Weilenmann C,Negroni JA

    更新日期:2013-07-01 00:00:00

  • Induction of antioxidant and detoxification response by oxidants in cardiomyocytes: evidence from gene expression profiling and activation of Nrf2 transcription factor.

    abstract::Mild or low doses of oxidants are known to prime cells towards resistance against further damage. In cardiomyocytes, we found that pretreatment with 100 microM H(2)O(2) prevents the cells from apoptosis induced by doxorubicin (Dox). Affymetrix microarray analyses of 28,000 genes reveal that H(2)O(2) treated cells redu...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2006.09.012

    authors: Purdom-Dickinson SE,Lin Y,Dedek M,Morrissy S,Johnson J,Chen QM

    更新日期:2007-01-01 00:00:00

  • Production of free radicals and lipid peroxides in early experimental myocardial ischemia.

    abstract::Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibil...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(83)90260-2

    authors: Rao PS,Cohen MV,Mueller HS

    更新日期:1983-10-01 00:00:00

  • Myocardial adenosine formation during hypoxia: effects of ecto-5'-nucleotidase inhibition.

    abstract::Release of adenosine and AMP into epicardial fluid and coronary venous effluent of isovolumic guinea-pig hearts was examined during normoxic (95% O2) and hypoxic (30% O2) perfusion with and without the ecto-5'-nucleotidase inhibitor alpha,beta-methylene adenosine diphosphate (AOPCP)*. Normoxic epicardial and venous ad...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(92)93166-h

    authors: Headrick JP,Matherne GP,Berne RM

    更新日期:1992-03-01 00:00:00

  • Alpha adrenergic receptor mechanism: biochemical events.

    abstract::Immediate post-receptor events following alpha-adrenoceptor stimulation in cardiac ventricular muscle are still largely unknown. Since membrane redox systems appear to be present in cell plasma membranes and may be involved in trans-sarcolemma electron efflux, the possibility that Ca2+ inflow was controlled by electro...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(86)80462-x

    authors: Clark MG,Rattigan S

    更新日期:1986-11-01 00:00:00

  • Phorbolester inhibits alpha 1-adrenoceptor mediated phosphoinositide breakdown in cardiomyocytes.

    abstract::The regulation of and the intracellular events following alpha 1-adrenergic receptor stimulation of myocardium are not completely understood. The alpha 1-adrenergic stimulation of phosphoinositide breakdown was examined in a culture of neonatal rat ventricular myocytes and the influence of a protein kinase C activator...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(89)90607-x

    authors: Meij JT,Lamers JM

    更新日期:1989-07-01 00:00:00

  • Cardiac morphogenetic defects and conduction abnormalities in mice homozygously deficient for connexin40 and heterozygously deficient for connexin45.

    abstract::Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity. We found that Cx40/Cx45 double deficiency (Cx40(-/-)/Cx45(+/-)) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth. The majority of Cx40(-/-)/C...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2006.07.005

    authors: Krüger O,Maxeiner S,Kim JS,van Rijen HV,de Bakker JM,Eckardt D,Tiemann K,Lewalter T,Ghanem A,Lüderitz B,Willecke K

    更新日期:2006-11-01 00:00:00

  • Mechanism of the positive inotropic effect of milrinone in cultured embryonic chick ventricular cells.

    abstract::Milrinone, a potent positive inotropic and vasodilating agent, has shown promise in the clinical treatment of congestive heart failure, but significant controversy about its mechanism of action exists. To approach these mechanistic problems in a non-innervated, non-diffusion-limited system, the effects of milrinone on...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(87)80548-5

    authors: Olson EM,Kim D,Smith TW,Marsh JD

    更新日期:1987-01-01 00:00:00

  • Generation of Fabry cardiomyopathy model for drug screening using induced pluripotent stem cell-derived cardiomyocytes from a female Fabry patient.

    abstract:BACKGROUND:Fabry disease is an X-linked disease caused by mutations in α-galactosidase A (GLA); these mutations result in the accumulation of its substrates, mainly globotriaosylceramide (Gb3). The accumulation of glycosphingolipids induces pathogenic changes in various organs, including the heart, and Fabry cardiomyop...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2018.07.246

    authors: Kuramoto Y,Naito AT,Tojo H,Sakai T,Ito M,Shibamoto M,Nakagawa A,Higo T,Okada K,Yamaguchi T,Lee JK,Miyagawa S,Sawa Y,Sakata Y,Komuro I

    更新日期:2018-08-01 00:00:00

  • Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing monocyte infiltration in Ldlr(-/-) mice.

    abstract:RATIONALE:Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE:We aimed to investigate the effect of sEH inhibition in at...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2016.08.001

    authors: Li D,Liu Y,Zhang X,Lv H,Pang W,Sun X,Gan LM,Hammock BD,Ai D,Zhu Y

    更新日期:2016-09-01 00:00:00

  • I(f) blocking potency of ivabradine is preserved under elevated endotoxin levels in human atrial myocytes.

    abstract::Lower heart rate is associated with better survival in patients with multiple organ dysfunction syndrome (MODS), a disease mostly caused by sepsis. The benefits of heart rate reduction by ivabradine during MODS are currently being investigated in the MODIfY clinical trial. Ivabradine is a selective inhibitor of the pa...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2014.02.010

    authors: Scheruebel S,Koyani CN,Hallström S,Lang P,Platzer D,Mächler H,Lohner K,Malle E,Zorn-Pauly K,Pelzmann B

    更新日期:2014-07-01 00:00:00

  • SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes.

    abstract::Sensitive to apoptosis gene (SAG) is a novel RING finger protein that has been shown to be involved in protection against apoptotic cell death induced by oxidative stress in various cell types. As SAG has been previously shown to be expressed in the heart, we assessed its role in cardiac myocytes exposed to ischaemic ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(03)00003-8

    authors: Chanalaris A,Sun Y,Latchman DS,Stephanou A

    更新日期:2003-03-01 00:00:00