Abstract:
RATIONALE:Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. OBJECTIVE:Here we addressed this question by investigating the role of cardiac sodium channels in zebrafish heart development. METHODS AND RESULTS:Transcripts of the functionally-conserved Scn5a homologs scn5Laa and scn5Lab were detected in the gastrulating zebrafish embryo and subsequently in the embryonic myocardium. Antisense knockdown of either channel resulted in marked cardiac chamber dysmorphogenesis and perturbed looping. These abnormalities were associated with decreased expression of the myocardial precursor genes nkx2.5, gata4, and hand2 in anterior lateral mesoderm and significant deficits in the production of cardiomyocyte progenitors. These early defects did not appear to result from altered membrane electrophysiology, as prolonged pharmacological blockade of sodium current failed to phenocopy channel knockdown. Moreover, embryos grown in calcium channel blocker-containing medium had hearts that did not beat but developed normally. CONCLUSIONS:These findings identify a novel and possibly nonelectrogenic role for cardiac sodium channels in heart development.
journal_name
Circ Resjournal_title
Circulation researchauthors
Chopra SS,Stroud DM,Watanabe H,Bennett JS,Burns CG,Wells KS,Yang T,Zhong TP,Roden DMdoi
10.1161/CIRCRESAHA.109.213132subject
Has Abstractpub_date
2010-04-30 00:00:00pages
1342-50issue
8eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.109.213132journal_volume
106pub_type
杂志文章abstract::Cell-cell communication has proven to be even more complex than previously thought since the discovery that extracellular vesicles serve as containers of biological information on various pathophysiological settings. Extracellular vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic bodies...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300858
更新日期:2014-01-17 00:00:00
abstract::We examined whether albumin-derived advanced glycosylation end products (AGEs) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic endothelial cells were observed when exposed to different concentrations of albumin-derived AGEs...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.3.e50
更新日期:2000-02-18 00:00:00
abstract::After cervical aortic nerve section, mean arterial pressure in the unanesthetized dog increased by an average of 7.4 mm Hg. Following a more extensive denervation of aortic arch receptors by section of intrathoracic vagal branches, arterial pressure increased by 16.7 mm Hg. The above changes were seen in the stable st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.1.26
更新日期:1979-07-01 00:00:00
abstract::Freshly dispersed rabbit ear artery cells were studied using patch-clamp techniques to measure membrane currents in whole cells and single-channel currents in membrane patches. Whole-cell calcium currents recorded at physiologic extracellular calcium concentrations were small (approximately 10 pA). Recordings with 110...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::We examined the function of the interventricular septum in six open-chest dogs by inserting piezoelectric crystals into the interventricular septum. Continuous ultrasonic recordings showed that the changes in myocardial chord length (MCL) in the septum and free walls of the right and left ventricle were similar during...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.1.52
更新日期:1981-07-01 00:00:00
abstract::During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicar...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150755
更新日期:2007-12-07 00:00:00
abstract::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.9.768
更新日期:2000-10-27 00:00:00
abstract::Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This o...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000259559.48597.32
更新日期:2007-03-02 00:00:00
abstract::Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focus...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307547
更新日期:2016-04-15 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::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300269
更新日期:2013-08-30 00:00:00
abstract::Electrocardiogram (ECG) electrodes and carotid arterial and superior vena caval (SVC) catheters were placed in eight nonpregnant ewes and 11 fetuses (109-129 days gestation) to measure heart rate, arterial presssure, P-R interval, left ventricular pre-ejection period (PEP), and left ventricular ejection time (LVET), b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.5.635
更新日期:1977-11-01 00:00:00
abstract::Cultured vascular endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferre...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000216595.15868.55
更新日期:2006-04-14 00:00:00
abstract::Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.593
更新日期:1992-03-01 00:00:00
abstract::Changes in cardiac filling pressure (central venous pressure) were measured following carotid occlusion and infusions of catecholamines in awake dogs while cardiac output was held constant. After carotid occlusion in dogs with vagi blocked, central venous pressure increased about 0.8 mm Hg (an estimated decrease in va...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.4.440
更新日期:1984-10-01 00:00:00
abstract::The effects of acute renovascular hypertension on the sympathetic nervous system, regional blood flow and cardiac function were studied in conscious dogs submitted to renal artery occlusion by inflation of a cuff implanted previously around one renal artery. We then compared the alterations in plasma renin and catecho...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.47.3.356
更新日期:1980-09-01 00:00:00
abstract::Cardiovascular disease is a major killer in postmenopausal women in the industrialized societies. To investigate the effect of progestogen and 17 beta-estradiol replacement therapy on atherogenesis, we studied 60 cholesterol-fed ovariectomized rabbits for 13 weeks. They were randomly assigned to four groups of 15 rabb...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.6.1198
更新日期:1992-06-01 00:00:00
abstract::The daily rate of cell replication in the aortic endothelium of the normal rat falls from a maximum of 13% at birth to 0.1-0.3% at age 5-6 months. This residual rate of replication largely represents the turnover rate of the endothelium in normal animals. After renal hypertension of 2-3 weeks duration, however, the ra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.2.248
更新日期:1977-08-01 00:00:00
abstract::Transcriptional thyroid hormone responsiveness of the cardiac alpha-myosin heavy chain (alpha-MHC) gene has been demonstrated in transfections into fetal and neonatal cardiomyocytes and in transgenic mice. However, the correspondence between the regulation of MHC expression in dissociated cells with that in the intact...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.6.1211
更新日期:1993-06-01 00:00:00
abstract::Vascular dysfunction in diabetes is attributed to lack of bioavailable nitric oxide (NO) and is postulated as a primary cause of small vessel complications as a result of poor glycemic control. Although it has been proposed that NO is bound by red blood cells (RBCs) and can induce relaxation of blood vessels distal to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000122044.21787.01
更新日期:2004-04-16 00:00:00
abstract::To elucidate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring alpha 1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.5.735
更新日期:1987-11-01 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::The kinetics of contractions and Ca(2+) transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca(2+) trans...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.11.1040
更新日期:2000-11-24 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 plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isom...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.4.289
更新日期:1976-04-01 00:00:00
abstract::We have shown previously that tyrosine 319 in a conserved YIPP motif in the C terminus of angiotensin II (Ang II) type 1 receptors (AT(1)Rs) is essential for transactivation of epidermal growth factor receptor (EGFR) in vitro. We hypothesized that the signaling mechanism mediated through the specific amino acid sequen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000240147.49390.61
更新日期:2006-09-01 00:00:00
abstract::Pyridine nucleotides are abundant soluble coenzymes and they undergo reversible oxidation and reduction in several biological electron-transfer reactions. They are comprised of two mononucleotides, adenosine monophosphate and nicotinamide mononucleotide, and are present as oxidized and reduced nicotinamide adenine din...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.247924
更新日期:2012-08-17 00:00:00
abstract::Transient coronary occlusion (15 minutes) does not result in irreversible myocardial injury but is associated with a depression of contractile function sustained for several hours to days ("stunned myocardium"). The defect in the contractile process responsible for this phenomenon has been suggested to be causally rel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.6.834
更新日期:1987-12-01 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::The subcellular distribution of cardiac muscarinic receptors was defined in canine ventricular myocardium, and receptors were solubilized from subcellular fractions enriched in muscarinic receptor content. The subcellular location of muscarinic receptors in cardiac tissue was determined by measurement of the distribut...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.6.664
更新日期:1983-06-01 00:00:00