Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia.

Abstract:

:Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca(2+) and H(+) and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tested the hypothesis that uncoupling induced by acute ischemia is associated with changes in phosphorylation of the major cardiac gap junction protein, connexin43 (Cx43). Adult rat hearts perfused on a Langendorff apparatus were subjected to ischemia or ischemia/reperfusion. Changes in coupling were monitored by measuring whole-tissue resistance. Changes in the amount and distribution of phosphorylated and nonphosphorylated isoforms of Cx43 were measured by immunoblotting and confocal immunofluorescence microscopy using isoform-specific antibodies. In control hearts, virtually all Cx43 identified immunohistochemically at apparent intercellular junctions was phosphorylated. During ischemia, however, Cx43 underwent progressive dephosphorylation with a time course similar to that of electrical uncoupling. The total amount of Cx43 did not change, but progressive reduction in total Cx43 immunofluorescent signal and concomitant accumulation of nonphosphorylated Cx43 signal occurred at sites of intercellular junctions. Functional recovery during reperfusion was associated with increased levels of phosphorylated Cx43. These observations suggest that uncoupling induced by ischemia is associated with dephosphorylation of Cx43, accumulation of nonphosphorylated Cx43 within gap junctions, and translocation of Cx43 from gap junctions into intracellular pools.

journal_name

Circ Res

journal_title

Circulation research

authors

Beardslee MA,Lerner DL,Tadros PN,Laing JG,Beyer EC,Yamada KA,Kléber AG,Schuessler RB,Saffitz JE

doi

10.1161/01.res.87.8.656

subject

Has Abstract

pub_date

2000-10-13 00:00:00

pages

656-62

issue

8

eissn

0009-7330

issn

1524-4571

journal_volume

87

pub_type

杂志文章
  • A 17mer peptide interferes with acidification-induced uncoupling of connexin43.

    abstract::Structure/function analysis shows that the carboxyl terminal (CT) domain of connexin43 (Cx43) is essential for the chemical regulation of cell-cell communication. Of particular interest is the region between amino acids 260 and 300. Structural preservation of this region is essential for acidification-induced uncoupli...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.9.929

    authors: Calero G,Kanemitsu M,Taffet SM,Lau AF,Delmar M

    更新日期:1998-05-18 00:00:00

  • Mechanisms that regulate macrophage burden in atherosclerosis.

    abstract::Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells. A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. Although technological advances are still nee...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.301174

    authors: Randolph GJ

    更新日期:2014-05-23 00:00:00

  • Prejunctional inhibition of norepinephrine release caused by acetylcholine in the human saphenous vein.

    abstract::We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.49.2.337

    authors: Rorie DK,Rusch NJ,Shepherd JT,Vanhoutte PM,Tyce GM

    更新日期:1981-08-01 00:00:00

  • Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels.

    abstract:RATIONALE:The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. OBJECTIVE:This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channe...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.197558

    authors: Gómez R,Caballero R,Barana A,Amorós I,Calvo E,López JA,Klein H,Vaquero M,Osuna L,Atienza F,Almendral J,Pinto A,Tamargo J,Delpón E

    更新日期:2009-08-14 00:00:00

  • Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle.

    abstract::Propagation in cardiac muscle is faster in the longitudinal than in the transverse axis of the cells. Yet, as a result of the larger upstroke velocity of action potentials propagating transversely, it has been suggested that longitudinal propagation is more vulnerable to block. To study the relation between conduction...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.60.5.780

    authors: Delmar M,Michaels DC,Johnson T,Jalife J

    更新日期:1987-05-01 00:00:00

  • The distribution of refractory periods influences the dynamics of ventricular fibrillation.

    abstract::The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In gui...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.88.5.e49

    authors: Choi BR,Liu T,Salama G

    更新日期:2001-03-16 00:00:00

  • Ca++ distribution after Na+ pump inhibition in cultured neonatal rat myocardial cells.

    abstract::The influence of inhibition of the Na+ pump, with secondary stimulation of Na+-Ca++ exchange, on cellular Ca++ distribution is examined using the on-line scintillation disk technique and cultured neonatal rat myocardial cells. Under control conditions, La+++ displaced 78.1 +/- 1.13% (SEM) of the total cell associated ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.51.5.543

    authors: Burt JM,Langer GA

    更新日期:1982-11-01 00:00:00

  • Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

    abstract::In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.59.2.178

    authors: Pagani M,Lombardi F,Guzzetti S,Rimoldi O,Furlan R,Pizzinelli P,Sandrone G,Malfatto G,Dell'Orto S,Piccaluga E

    更新日期:1986-08-01 00:00:00

  • L-type calcium channel blockers exert an antiinflammatory effect by suppressing expression of plasminogen receptors on macrophages.

    abstract::L-type Ca(2+) channel (LTCC) blockers, represented by amlodipine and verapamil, are widely used antihypertensive drugs that also have antiinflammatory activities. Plasminogen (Plg) is an important mediator of macrophage recruitment, and this role depends on its interaction with Plg receptors (Plg-Rs). Plg-Rs include h...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.200311

    authors: Das R,Burke T,Van Wagoner DR,Plow EF

    更新日期:2009-07-17 00:00:00

  • Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation.

    abstract:RATIONALE:Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. OBJECTIVE:The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.302439

    authors: Wang Y,Wang X,Lau WB,Yuan Y,Booth D,Li JJ,Scalia R,Preston K,Gao E,Koch W,Ma XL

    更新日期:2014-02-28 00:00:00

  • Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response.

    abstract::Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.3.504

    authors: Motte S,Pirotton S,Boeynaems JM

    更新日期:1993-03-01 00:00:00

  • Genetics of congenital heart disease: the glass half empty.

    abstract::Congenital heart disease (CHD) is the most common congenital anomaly in newborn babies. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the developmental pathways involved in myocyte specification, differentiation, or cardiac morphogene...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.112.300853

    authors: Fahed AC,Gelb BD,Seidman JG,Seidman CE

    更新日期:2013-02-15 00:00:00

  • Stable expression and coupling of cardiac L-type Ca2+ channels with beta 1-adrenoceptors.

    abstract::A number of neurotransmitters modulate cardiac dihydropyridine-sensitive L-type Ca2+ channels through several homologous G protein-coupled receptors. Previous studies that have examined receptor-Ca2+ channel interactions have suffered because of the coexpression of various receptor subtypes in native cells. To study t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.76.3.335

    authors: Yatani A,Wakamori M,Niidome T,Yamamoto S,Tanaka I,Mori Y,Katayama K,Green S

    更新日期:1995-03-01 00:00:00

  • Relationship between structure and fatty acid metabolism in mitochondria isolated from ischemic rat hearts.

    abstract::We studied mitochondrial structure and intermediates of fatty acid metabolism in mitochondria isolated from ischemic hearts. By electron microscopy, no structural difference was detected between mitochondria isolated from control hearts and from ischemic hearts receiving glucose as the only substrate. However, major d...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.5.740

    authors: Feuvray D,Plouët J

    更新日期:1981-05-01 00:00:00

  • Dominant-negative control of cAMP-dependent IKs upregulation in human long-QT syndrome type 1.

    abstract:RATIONALE:The mutation A341V in the S6 transmembrane segment of KCNQ1, the α-subunit of the slowly activating delayed-rectifier K(+) (I(Ks)) channel, predisposes to a severe long-QT1 syndrome with sympathetic-triggered ventricular tachyarrhythmias and sudden cardiac death. OBJECTIVE:Several genetic risk modifiers have...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.249482

    authors: Heijman J,Spätjens RL,Seyen SR,Lentink V,Kuijpers HJ,Boulet IR,de Windt LJ,David M,Volders PG

    更新日期:2012-01-20 00:00:00

  • Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.

    abstract::In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.1.101

    authors: Myers BD,Deen WM,Brenner BM

    更新日期:1975-07-01 00:00:00

  • Vanadate effect on the Na,K-ATPase and the Na-K pump in in vitro-grown rat vascular smooth muscle cells.

    abstract::The impact of vanadate on the Na,K-ATPase system in the vascular smooth muscle cell is poorly understood. The present study describes the kinetics of the effect of vanadate on Na,K-ATPase and the Na-K pump in in vitro grown rat VSMC's. Vanadate interaction with the Na,K-ATPase system in vascular smooth muscle cells wa...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.53.2.186

    authors: Searle BM,Higashino H,Khalil F,Bogden JD,Tokushige A,Tamura H,Kino M,Aviv A

    更新日期:1983-08-01 00:00:00

  • NHLBI-Sponsored Randomized Trial of Postconditioning During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

    abstract:RATIONALE:Postconditioning at the time of primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction may reduce infarct size and improve myocardial salvage. However, clinical trials have shown inconsistent benefit. OBJECTIVE:We performed the first National Heart, Lung, and Blood In...

    journal_title:Circulation research

    pub_type: 杂志文章,随机对照试验

    doi:10.1161/CIRCRESAHA.118.314060

    authors: Traverse JH,Swingen CM,Henry TD,Fox J,Wang YL,Chavez IJ,Lips DL,Lesser JR,Pedersen WR,Burke NM,Pai A,Lindberg JL,Garberich RF

    更新日期:2019-03-01 00:00:00

  • Potentiation by hypercholesterolemia of the induction of aortic intramural synthesis of plasminogen activator inhibitor type 1 by endothelial injury.

    abstract::Accumulation of plasminogen activator inhibitor type 1 (PAI-1) in the arterial wall may accelerate atherogenesis by inhibiting fibrinolysis, diminishing proteolysis of extracellular matrix proteins, or modifying migration of vascular smooth muscle cells. Increased intramural expression of the PAI-1 gene is induced by ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.4.671

    authors: Sawa H,Sobel BE,Fujii S

    更新日期:1993-10-01 00:00:00

  • High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system.

    abstract::Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained u...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.10.929

    authors: Tamaddon HS,Vaidya D,Simon AM,Paul DL,Jalife J,Morley GE

    更新日期:2000-11-10 00:00:00

  • Mechanisms of plaque formation and rupture.

    abstract::Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.302721

    authors: Bentzon JF,Otsuka F,Virmani R,Falk E

    更新日期:2014-06-06 00:00:00

  • Morphometry of pinocytotic vesicles in the capillary endothelium of rabbit lungs using automated equipment.

    abstract::Pinocytotic vesicles are one of several anatomic factors relevant to the permeability for macromolecules of capillary endothelia. We quantitified the number and distribution of pinocytotic vesicles present in the endothelium of pulmonary capillaries. Several similar studies have been reported in the past for endotheli...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.47.3.384

    authors: Gil J,Silage DA

    更新日期:1980-09-01 00:00:00

  • Long-Term Outcome of Administration of c-kit(POS) Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do not Become Cardiomyocytes, but Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at L

    abstract:RATIONALE:Cardiac progenitor cells (CPCs) improve left ventricular remodeling and function after acute or chronic myocardial infarction. However, the long-term (>5 weeks) effects, potential tumorigenicity, and fate of transplanted CPCs are unknown. OBJECTIVE:To assess the outcome of CPC therapy at 1 year. METHODS AND...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307647

    authors: Tang XL,Li Q,Rokosh G,Sanganalmath SK,Chen N,Ou Q,Stowers H,Hunt G,Bolli R

    更新日期:2016-04-01 00:00:00

  • Limitations of the double sucrose gap voltage clamp technique in tension-voltage determinations on frog atrial muscle.

    abstract::The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inwa...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.1.106

    authors: Tarr M,Trank JW

    更新日期:1976-07-01 00:00:00

  • Oscillatory afterpotentials in dog ventricular muscle fibers.

    abstract::Ventricular muscle fibers from dog hearts were superfused with K+-free, high Ca2+ solutions after exposure to a K+-free, Ca2+-free superfusate. Following a series of driven action potentials, oscillatory after potentials (OAPs) were elicited in all 40 preparations at a resting potential of greater than -60 mV. The OAP...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.4.510

    authors: Hiraoka M,Okamoto Y,Sano T

    更新日期:1981-04-01 00:00:00

  • Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in x-ray-irradiated hypercholesterolemic pigs.

    abstract::To assess whether coronary spasm affects the progression of atherosclerosis and results in evolution of myocardial infarction, the role of coronary spasm on the fine structure of conduit coronary arteries was studied morphologically. Göttingen miniature pigs were fed a semisynthetic diet containing 2% cholesterol and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.2.272

    authors: Nagasawa K,Tomoike H,Hayashi Y,Yamada A,Yamamoto T,Nakamura M

    更新日期:1989-08-01 00:00:00

  • Cardiac sympathetic afferent cell bodies are located in the peripheral nervous system of the cat.

    abstract::Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic i...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.3.554

    authors: Bosnjak ZJ,Kampine JP

    更新日期:1989-03-01 00:00:00

  • Aging and Autophagy in the Heart.

    abstract::The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypert...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.307474

    authors: Shirakabe A,Ikeda Y,Sciarretta S,Zablocki DK,Sadoshima J

    更新日期:2016-05-13 00:00:00

  • Angiogenesis and pericytes in the initiation of ectopic calcification.

    abstract::Ectopic calcification of blood vessels, heart valves, and skeletal muscle is a major clinical problem. There is now good evidence that angiogenesis is associated with ectopic calcification in these tissues and that it is necessary, but not sufficient, for calcification to occur. Angiogenesis may regulate ectopic calci...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000163634.51301.0d

    authors: Collett GD,Canfield AE

    更新日期:2005-05-13 00:00:00

  • Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction.

    abstract:RATIONALE:Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs. OBJECTIVE:We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction. METHODS AND RESULTS:Depletion of N...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.302625

    authors: Yan X,Hegab AE,Endo J,Anzai A,Matsuhashi T,Katsumata Y,Ito K,Yamamoto T,Betsuyaku T,Shinmura K,Shen W,Vivier E,Fukuda K,Sano M

    更新日期:2014-02-14 00:00:00