Abstract:
:The cardiac high molecular weight proteins/ryanodine receptors were purified to homogeneity from junctional sarcoplasmic reticulum membranes and shown to exhibit large conductance calcium channel activity. High molecular weight proteins were solubilized from junctional sarcoplasmic reticulum in zwitterionic detergent and purified by size-exclusion chromatography followed by sucrose density gradient centrifugation. The purified proteins exhibited an apparent Mr = 400,000-350,000, and bound [3H]ryanodine with a Kd of 4.6 nM and a Bmax of 140-280 pmol/mg protein. High molecular weight proteins demonstrated divalent cation channel activity after incorporation into planar lipid bilayers. Two channel types were identified. Large conductance channels had a slope conductance of 96 +/- 13 pS and a Erev of 42 +/- 9 mV (n = 5); small conductance channels had a slope conductance of 5.5 +/- 1 pS [1.0 microM cis CaCl2; 50 mM trans Ba(OH)2]. Reducing cis calcium from 1 microM to 1 nM reduced the large conductance channel open time from 7 +/- 1% to 0.1% (holding potential, -100 mV). Adding ATP (1 mM) to the cis chamber increased channel open time from 6 +/- 1% to 52 +/- 4% (holding potential, -100 mV); 10 nM ryanodine increased and 100 microM ryanodine decreased percent of open time of the 96 pS channel, without altering unitary channel conductance. The large conductance channel was similar to the calcium release channel detected in native canine cardiac junctional sarcoplasmic reticulum vesicles. Our data suggest that the ryanodine receptor, the calcium-release channel, and the high molecular weight proteins are all identical proteins containing allosteric regulatory sites for calcium, ATP, and ryanodine.
journal_name
Circ Resjournal_title
Circulation researchauthors
Rardon DP,Cefali DC,Mitchell RD,Seiler SM,Jones LRdoi
10.1161/01.res.64.4.779subject
Has Abstractpub_date
1989-04-01 00:00:00pages
779-89issue
4eissn
0009-7330issn
1524-4571journal_volume
64pub_type
杂志文章abstract::Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiograph...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000016960.61087.86
更新日期:2002-05-03 00:00:00
abstract:RATIONALE:It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE:The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS:In 110 patients with systolic heart failu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307765
更新日期:2016-04-15 00:00:00
abstract::We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 micron) using microapplication into the perivascular space. Concentration-response curves for histamine showed dilations which started at 10(-7) M and were maximal at 10(-5) and 10(-4) M. The H2 blocker, cimetidine, induc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.2.161
更新日期:1979-02-01 00:00:00
abstract::alpha-Adrenergic receptor stimulation regulates the activity of a number of different cardiac ion channels, including those underlying one or more distinct Cl- conductances. The whole-cell patch-clamp technique was used in the present study to investigate the effects of alpha-adrenergic stimulation on the beta-adrener...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.6.1090
更新日期:1996-06-01 00:00:00
abstract::To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 month...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.536
更新日期:1996-04-01 00:00:00
abstract::The aim of this study was to examine the effect of exercise training on reflex control of vascular resistance in human males. Forearm vascular responses to lower body negative pressure (LBNP) at -10 and -40 mm Hg were compared between highly trained young athletes (21.5 +/- 0.5 years old, n = 14) and age-matched nonat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.59.1.43
更新日期:1986-07-01 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 atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192443
更新日期:2009-07-02 00:00:00
abstract:RATIONALE:Myocardial infarction (MI) results in loss of cardiac myocytes in the ischemic zone of the heart, followed by fibrosis and scar formation, which diminish cardiac contractility and impede angiogenesis and repair. Myofibroblasts, a specialized cell type that switches from a fibroblast-like state to a contractil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.223172
更新日期:2010-07-23 00:00:00
abstract::Nitric oxide (NO) decreases cellular oxygen (O(2)) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O(2) consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.197228
更新日期:2009-05-22 00:00:00
abstract::Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000338597.71702.ad
更新日期:2008-11-21 00:00:00
abstract::Local alterations in the hemodynamic environment regulate endothelial cell function, but the signal-transduction mechanisms involved in this process remain unclear. Because mitogen-activated protein (MAP) kinases have been shown to be activated by physical forces, we measured the phosphorylation and enzyme activity of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.5.869
更新日期:1995-11-01 00:00:00
abstract::We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion. Occlusion of the left anterior descending coronary artery for 2 hours followed by 4 hours of reperfusion in anesthetized cats results in a large washout of creatin...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.3.621
更新日期:1988-09-01 00:00:00
abstract::The effect of hypercapnia on coronary vascular resistance (CVR) was studied in seven open-chest dogs. Coronary blood flow was supplied to the cannulated left main coronary artery from the femoral artery by a precision pump. Coronary arterial PCO2 was locally controlled with a small membrane oxygenator in the coronary ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.4.558
更新日期:1976-10-01 00:00:00
abstract::Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000102937.50486.1B
更新日期:2003-11-28 00:00:00
abstract::Ablation of the enzyme phosphoinositide 3-kinase (PI3K)gamma (PI3Kgamma(-/-)) in mice increases cardiac contractility by elevating intracellular cAMP and enhancing sarcoplasmic reticulum Ca(2+) handling. Because cAMP is a critical determinant of heart rate, we investigated whether heart rate is altered in mice lacking...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.158428
更新日期:2007-12-07 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::Ischemia/reperfusion (I/R) affects the integrity of the endoplasmic reticulum (ER), the site of synthesis and folding of numerous proteins. Therefore, I/R may activate the unfolded protein response (UPR), resulting in the induction of a collection of ER stress proteins, many of which are protective and function to res...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000220643.65941.8d
更新日期:2006-05-12 00:00:00
abstract::Cyclic nucleotide phosphodiesterases regulate cAMP-mediated signaling by controlling intracellular cAMP content. The cAMP-hydrolyzing activity of several families of cyclic nucleotide phosphodiesterases found in human heart is regulated by cGMP. In the case of PDE2, this regulation primarily involves the allosteric st...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.106.144501
更新日期:2007-06-08 00:00:00
abstract::Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-ma...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.5.975
更新日期:1988-05-01 00:00:00
abstract::The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.194506
更新日期:2009-05-08 00:00:00
abstract:RATIONALE:ATP-binding cassette transporter A1 (ABCA1) plays a critical role in eliminating excess free cholesterol from tissues by effluxing cellular free cholesterol and phospholipids to lipid-poor apolipoprotein AI. Macrophage ABCA1 also dampens proinflammatory myeloid differentiation primary-response protein 88-depe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.269043
更新日期:2012-11-09 00:00:00
abstract::Early afterdepolarizations (EADs) are a type of triggered activity found in heart muscle. We used voltage-clamped sheep cardiac Purkinje fibers to examine the mechanism underlying EADs induced near action potential plateau voltages with the Ca2+ current agonist Bay K 8644 and the effect of several interventions known ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.5.977
更新日期:1989-05-01 00:00:00
abstract::Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants li...
journal_title:Circulation research
pub_type: 评审
doi:10.1161/CIRCRESAHA.120.316574
更新日期:2020-06-19 00:00:00
abstract::Although peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have an antihypertensive effect in vivo, the precise mechanism has not been fully elucidated. We examined their effects on Rho/Rho kinase pathway, a key regulator of vascular tone. In cultured rat aortic smooth muscle cells (RASMC), Rho kina...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000142313.68389.92
更新日期:2004-09-03 00:00:00
abstract::The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.6.864
更新日期:1985-12-01 00:00:00
abstract::A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present stud...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosol...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000262653.84850.8b
更新日期:2007-04-13 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::Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.233403
更新日期:2012-01-20 00:00:00