Abstract:
AIMS:KCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K(+) channel responsible for I(Ks)-a major repolarizing current in the human heart-and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known and undefined regulatory proteins. Thus, identification of proteins that modulate its biosynthesis, localization, activity, and/or degradation is of great interest from both a physiological and pathological point of view. METHODS AND RESULTS:Using a yeast two-hybrid screening, we detected a direct interaction between beta-tubulin and the KCNQ1 N-terminus. The interaction was confirmed by co-immunoprecipitation of beta-tubulin and KCNQ1 in transfected COS-7 cells and in guinea pig cardiomyocytes. Using immunocytochemistry, we also found that they co-localized in cardiomyocytes. We tested the effects of microtubule-disrupting and -stabilizing agents (colchicine and taxol, respectively) on the KCNQ1-KCNE1 channel activity in COS-7 cells by means of the permeabilized-patch configuration of the patch-clamp technique. None of these agents altered I(Ks). In addition, colchicine did not modify the current response to osmotic challenge. On the other hand, the I(Ks) response to protein kinase A (PKA)-mediated stimulation depended on microtubule polymerization in COS-7 cells and in cardiomyocytes. Strikingly, KCNQ1 channel and Yotiao phosphorylation by PKA-detected by phospho-specific antibodies-was maintained, as was the association of the two partners. CONCLUSION:We propose that the KCNQ1-KCNE1 channel directly interacts with microtubules and that this interaction plays a major role in coupling PKA-dependent phosphorylation of KCNQ1 with I(Ks) activation.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Nicolas CS,Park KH,El Harchi A,Camonis J,Kass RS,Escande D,Mérot J,Loussouarn G,Le Bouffant F,Baró Idoi
10.1093/cvr/cvn085subject
Has Abstractpub_date
2008-08-01 00:00:00pages
427-35issue
3eissn
0008-6363issn
1755-3245pii
cvn085journal_volume
79pub_type
杂志文章abstract:AIMS:Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS:Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naï...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz102
更新日期:2020-02-01 00:00:00
abstract::Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic car...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz162
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVES:Myostatin, a member of the transforming growth factor-beta (TGF-beta) family, plays a key role in skeletal muscle myogenesis by limiting hyperplastic and hypertrophic muscle growth. In cardiac muscle, myostatin has been shown to limit agonist-induced cardiac hypertrophic growth. However, its role in cardiac ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.02.023
更新日期:2007-05-01 00:00:00
abstract::Zero drift may be a cause of imprecision when micromanometer tipped catheters are used for intravascular pressure measurement over long periods of time. Drift of only a few mm Hg may represent a significant error when accurate recording of low vascular pressures is required. To overcome this problem a micromanometer t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.2.152
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.021
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVES:Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract:AIMS:Cathepsin-L (CTSL) is a member of the lysozomal cysteine protease family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of CTSL in cardiac remodelling post-infarction. METHODS AND RESULTS:Experimental myocardial infarction (MI) was created in CTSL-defi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq328
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS:Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril suppl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00239-4
更新日期:1999-12-01 00:00:00
abstract:AIMS:To determine the role of gap junctions (GJs) in hypoxic pulmonary vasoconstriction (HPV). METHODS AND RESULTS:Studies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F2α...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt129
更新日期:2013-08-01 00:00:00
abstract:AIMS:The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may c...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu152
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVES:Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been qu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00218-0
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:Important physiological and pathophysiological conditions are associated with changes in secretion and synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The aim of this study was to examine the effects of mechanical stretch and endothelin-1 on ANF and BNP secretion and gene exp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.10.1519
更新日期:1994-10-01 00:00:00
abstract::STUDY OBJECTIVE - The objective was to measure platelet function in vivo (as cutaneous bleeding time), the role of catecholamines, and the effect of inhibiting thromboxane synthesis on bleeding time, in patients with myocardial infarction, unstable angina, and non-cardiac chest pain. DESIGN - Haemotological variables ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.1.19
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:Early thrombolysis can reduce infarct size and enhance the long term recovery of contractile function after acute myocardial infarction. These benefits of early reperfusion may be confounded, however, by platelet mediated reocclusion after initial lysis, and "reperfusion injury" mediated by oxygen derived fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.925
更新日期:1993-06-01 00:00:00
abstract::The progress made in our understanding of the pathophysiology and treatment of congestive heart failure (CHF) would not have been possible without a number of animal models of heart failure and hypertrophy, each one having unique advantages as well as disadvantages. The species and interventions used to create CHF dep...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(98)00110-2
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate whether infusion of either atrial natriuretic factor (ANF, 800 ng.h-1.rat-1) or a specific inhibitory of neutral endopeptidase 24.11 (NEI, UK 73,967, 5.4 mg.kg-1.d-1) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia. METHODS:Male Wist...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.4.519
更新日期:1994-04-01 00:00:00
abstract::As the developing heart grows and the chamber walls thicken, passive diffusion of oxygen and nutrients is replaced by a vascular plexus which remodels and expands to form a mature coronary vascular system. The coronary arteries and veins ensure the continued development of the heart and facilitate cardiac output with ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr035
更新日期:2011-07-15 00:00:00
abstract:AIMS:Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn140
更新日期:2008-09-01 00:00:00
abstract::Gender has an important influence on blood pressure, with premenopausal women having a lower arterial blood pressure than age-matched men. Compared with premenopausal women, postmenopausal women have higher blood pressures, suggesting that ovarian hormones may modulate blood pressure. However, whether sex hormones are...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00527-2
更新日期:2002-02-15 00:00:00
abstract:OBJECTIVE:After-depolarization associated arrhythmias are frequently observed in heart failure and associated with spontaneous calcium release from sarcoplasmic reticulum (SR), calcium after-transients. We hypothesize that disturbed SR calcium handling underlies calcium after-transients in heart failure (HF). METHODS:...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00854-4
更新日期:2003-04-01 00:00:00
abstract::Acute coronary syndromes result from fissure, erosion or rupture of a vulnerable atherosclerotic plaque. The characteristics of a vulnerable plaque include a large lipid pool, an abundance of inflammatory cells and mediators, a reduced smooth muscle cell and collagen content and a thin overlying fibrous cap. Potential...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(98)00279-x
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVES:The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. METHODS:Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaem...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.312
更新日期:1994-03-01 00:00:00
abstract:AIMS:TGF-β regulates tissue fibrosis: TGF-β promotes fibrosis, whereas bone morphogenetic protein (BMP)-7 is antifibrotic. To demonstrate that (i) left ventricular (LV) remodelling after pressure overload is associated with disequilibrium in the signalling mediated by these cytokines, and (ii) BMP-7 exerts beneficial e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw076
更新日期:2016-06-01 00:00:00
abstract::Angiotensin II has been implicated as an important factor in cardiac remodeling, particularly in the development of pathological left ventricular hypertrophy. It is generally assumed that angiotensin II is able to alter the phenotype of cardiac myocytes and fibroblasts, and several experiments have suggested that this...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00448-5
更新日期:2002-02-01 00:00:00
abstract::Blood vessels are permanently exposed to stretch and shear stress due to blood pressure and blood flow. Significant variations in the mechanical environment, of physiological or pathophysiological nature, occur in vivo. These trigger acute changes in vessel diameter that tend to restore basal levels of tensile and she...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.05.008
更新日期:2006-07-15 00:00:00
abstract::Most studies on stem cell transplantation therapy on myocardially infarcted animal models and phase-I human clinical trials have focused on the use of undifferentiated stem cells. There is a strong possibility that some degree of cardiomyogenic differentiation of stem cells in vitro prior to transplantation would resu...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2003.12.022
更新日期:2004-04-01 00:00:00
abstract::This study has investigated the origin of the pulsatile expansion of the forearm recorded by the amplification of the pulsatile signal derived from a mercury in rubber plethysmograph. Venous occlusion to pressures of 40 mmHg had no effect on the amplitude of the volume pulse, suggesting that the volume pulse originate...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.11.651
更新日期:1984-11-01 00:00:00
abstract:AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp043
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1093/cvr/27.8.1477
更新日期:1993-08-01 00:00:00