Abstract:
:Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1, one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show here that mice with deletion of the KCNQ1 protein partner KCNE1 have spontaneous episodes of atrial fibrillation despite normal atrial size and structure. Isoproterenol abolishes these abnormalities, but vagomimetic interventions have no effect. Whereas loss of KCNE1 function prolongs ventricular action potentials in humans, KCNE1-/- mice displayed unexpectedly shortened atrial action potentials, and multiple potential mechanisms were identified: (1) K+ currents (total and those sensitive to the KCNQ1 blocker chromanol 293B) were significantly increased in atrial cells from KCNE1-/- mice compared with controls, and (2) when CHO cells expressing KCNQ1 and KCNE1 were pulsed very rapidly (at rates comparable to the normal mouse heart and to human atrial fibrillation), the sigmoidicity of IKs activation prevented current accumulation, whereas cells expressing KCNQ1 alone displayed marked current accumulation at these very rapid rates. Thus, KCNE1 deletion in mice unexpectedly leads to increased outward current in atrial myocytes, shortens atrial action potentials, and enhances susceptibility to atrial fibrillation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Temple J,Frias P,Rottman J,Yang T,Wu Y,Verheijck EE,Zhang W,Siprachanh C,Kanki H,Atkinson JB,King P,Anderson ME,Kupershmidt S,Roden DMdoi
10.1161/01.RES.0000173047.42236.88subject
Has Abstractpub_date
2005-07-08 00:00:00pages
62-9issue
1eissn
0009-7330issn
1524-4571pii
01.RES.0000173047.42236.88journal_volume
97pub_type
杂志文章abstract::This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. C...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.4.922
更新日期:1991-04-01 00:00:00
abstract::The identification of nitric oxide ((*)NO) as an endogenously produced free radical mediator of endothelial-dependent relaxation and host defense has fundamentally changed concepts of cell signal transduction. Ligand-receptor oriented paradigms of cell signaling were originally centered on the concept of a high affini...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.202077
更新日期:2009-09-11 00:00:00
abstract::To determine the time course of efferent sympathetic denervation after transmural myocardial infarction (TMI) and of efferent vagal denervation after transmural or nontransmural myocardial infarction (NTMI), we measured effective refractory periods (ERP) basal and apical to TMI or NTMI in secobarbital-anesthetized, op...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.6.1111
更新日期:1988-06-01 00:00:00
abstract::The sinoatrial node, which resides at the junction of the right atrium and the superior caval vein, contains specialized myocardial cells that initiate the heart beat. Despite this fundamental role in heart function, the embryonic origin and mechanisms of localized formation of the sinoatrial node have not been define...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000258019.74591.b3
更新日期:2007-02-16 00:00:00
abstract::A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.8
更新日期:1975-01-01 00:00:00
abstract::The myocardium contains collagen matrix that is a major determinant of its architecture, structural integrity, and mechanical properties. This fibrillar matrix consists primarily of type I and type III collagens having epimysial, perimysial, and endomysial components. The present study shows the alteration of collagen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1474
更新日期:1990-12-01 00:00:00
abstract::Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000133247.69803.c3
更新日期:2004-07-09 00:00:00
abstract::Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.1.42
更新日期:1987-07-01 00:00:00
abstract::Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell-derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000132279.99249.f4
更新日期:2004-06-25 00:00:00
abstract::The epicardium, the tissue layer covering the cardiac muscle (myocardium), develops from the proepicardium, a mass of coelomic progenitors located at the venous pole of the embryonic heart. Proepicardium cells attach to and spread over the myocardium to form the primitive epicardial epithelium. The epicardium subseque...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.245589
更新日期:2011-12-09 00:00:00
abstract::In the early (3-day) stage of development, long-lasting openings of the L-type Ca2+ channels (mode 2) occur in embryonic chick heart cells. Since mode-2 behavior is infrequently observed in adult heart cells of other species, in the present study, developmental change in behavior of the Ca2+ channel was examined in yo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.376
更新日期:1992-08-01 00:00:00
abstract::Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were perf...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.166
更新日期:1990-07-01 00:00:00
abstract::The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000155964.34150.F7
更新日期:2005-02-18 00:00:00
abstract::The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.2.172
更新日期:1977-08-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9(-/-) mice). A denudi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000040420.17366.2e
更新日期:2002-11-01 00:00:00
abstract::Inwardly rectifying K+ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000218776.87842.43
更新日期:2006-04-28 00:00:00
abstract::Two NO synthase (NOS) isoforms have been described in vessels, an endothelial constitutive NOS (eNOS) and an inducible NOS (iNOS). The purpose of the present study was to examine the endothelium-dependent and endothelium-independent hypotensive response in aging rats, analyzing the ability of their vessels to produce ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.3.279
更新日期:1998-08-10 00:00:00
abstract::To delineate more clearly the importance of altered monovalent cation transport rate in the mediation of the positive inotropic effects of cardiac glycosides, we studied changes in the contractile state and rate of uptake of K+ and Rb+ by monolayer cultures of chick embryo ventricular cells during exposure to and wash...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.1.141
更新日期:1981-07-01 00:00:00
abstract::RhoA and Rac1 regulate formation of stress fibers and intercellular junctions, thus modulating endothelial monolayer permeability. Posttranslational modifications of RhoA and Rac1 regulate enzyme activity and subcellular localization, resulting in altered cellular function. The role of RhoA and Rac1 carboxyl methylati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000113923.85084.C1
更新日期:2004-02-20 00:00:00
abstract::The adenosine analogue phenylisopropyladenosine decreased the basal and isoproterenol-stimulated contractile state of isolated rat left atria. The ED50 levels for both responses were similar, suggesting that direct and antiadrenergic effects may be mediated by the same receptor. Phenylisopropyladenosine decreased the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.5.728
更新日期:1985-05-01 00:00:00
abstract::The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 min...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.6.1193
更新日期:1993-12-01 00:00:00
abstract:RATIONALE:A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE:To investiga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315833
更新日期:2019-12-06 00:00:00
abstract::Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1324
更新日期:1992-12-01 00:00:00
abstract::Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Incre...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.197996
更新日期:2009-06-05 00:00:00
abstract::The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000059562.91384.1A
更新日期:2003-03-07 00:00:00
abstract::Rat lungs were inflated and incubated in either anionic or cationic ferritin, and alveolar and capillary basement membranes were examined by electron microscopy. Cationic ferritin bound to heparan sulfate proteoglycans on the external surface of the alveolar basement membrane, whereas cationic ferritin bound to the la...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.2.155
更新日期:1984-08-01 00:00:00
abstract::Atherosclerotic plaque rupture is the main cause of coronary thrombosis and myocardial infarcts. Currently, there is no animal model of plaque disruption. We have developed a rabbit model in which an atherosclerotic plaque can be ruptured at will after an inflatable balloon becomes embedded into the plaque. Furthermor...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.7.705
更新日期:1998-10-05 00:00:00
abstract::The purpose of this study was to determine whether biphasic restitution of action potential duration (APD) in ventricular muscle permits the development of complex dynamic behavior. Such behavior is expected because of the steep ascending slope of restitution and the presence of a maximum. Action potentials recorded f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.5.915
更新日期:1995-05-01 00:00:00
abstract::Large conductance Ca(2+)-activated K(+) channels (BK(Ca)) play a critical role in blood pressure regulation by tuning the vascular smooth muscle tone, and hyposensitivity of BK(Ca) to Ca(2+) sparks resulting from its altered beta1 subunit stoichiometry underlies vasoconstriction in animal models of hypertension. Here ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.157271
更新日期:2007-08-31 00:00:00
abstract::Experiments were performed to investigate whether balloon injury induces nitric oxide synthase activity in the blood vessel wall. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and excised either immediately (t = 0), 6, or 24 hours after t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.331
更新日期:1992-08-01 00:00:00