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 Resjournal_title
Circulation researchauthors
Beardslee MA,Lerner DL,Tadros PN,Laing JG,Beyer EC,Yamada KA,Kléber AG,Schuessler RB,Saffitz JEdoi
10.1161/01.res.87.8.656subject
Has Abstractpub_date
2000-10-13 00:00:00pages
656-62issue
8eissn
0009-7330issn
1524-4571journal_volume
87pub_type
杂志文章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
更新日期:1998-05-18 00:00:00
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
更新日期:2014-05-23 00:00:00
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
更新日期:1981-08-01 00:00:00
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
更新日期:2009-08-14 00:00:00
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
更新日期:1987-05-01 00:00:00
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
更新日期:2001-03-16 00:00:00
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
更新日期:1982-11-01 00:00:00
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...
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pub_type: 杂志文章
doi:10.1161/01.res.59.2.178
更新日期:1986-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.200311
更新日期:2009-07-17 00:00:00
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更新日期:2014-02-28 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.72.3.504
更新日期:1993-03-01 00:00:00
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...
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pub_type: 杂志文章,评审
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更新日期:2013-02-15 00:00:00
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
更新日期:1995-03-01 00:00:00
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
更新日期:1981-05-01 00:00:00
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
更新日期:2012-01-20 00:00:00
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
更新日期:1975-07-01 00:00:00
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
更新日期:1983-08-01 00:00:00
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
更新日期:2019-03-01 00:00:00
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
更新日期:1993-10-01 00:00:00
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
更新日期:2000-11-10 00:00:00
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
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更新日期:2014-06-06 00:00:00
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
更新日期:1980-09-01 00:00:00
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...
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更新日期:2016-04-01 00:00:00
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
更新日期:1976-07-01 00:00:00
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
更新日期:1981-04-01 00:00:00
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
更新日期:1989-08-01 00:00:00
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
更新日期:1989-03-01 00:00:00
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
更新日期:2016-05-13 00:00:00
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
更新日期:2005-05-13 00:00:00
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
更新日期:2014-02-14 00:00:00