Abstract:
:Heptanol blocks sodium current (INa) in nerve, but its effects on cardiac INa have not been well characterized. Block of INa by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described by a single-site binding curve with half block at 1.3 mM (20 degrees C) and showed no "use dependence." With 1.5 mM heptanol, block increased slightly by 0.7%/degrees C from 10 degrees C to 27 degrees C. With 3.0 mM heptanol, steady-state availability shifted by 9.4 +/- 1.3 mV (n = 6) in the hyperpolarizing direction, and steady-state activation shifted by 8.3 +/- 2.2 mV (n = 5) in the depolarizing direction, thus closing off the INa "window current." Heptanol also decreased the time to peak and accelerated the decay of INa. Similar results were found with octanol at lower concentrations. These alcohols have important effects on cardiac INa at concentrations used in studies for cellular uncoupling in heart.
journal_name
Circ Resjournal_title
Circulation researchauthors
Nelson WL,Makielski JCdoi
10.1161/01.res.68.4.977subject
Has Abstractpub_date
1991-04-01 00:00:00pages
977-83issue
4eissn
0009-7330issn
1524-4571journal_volume
68pub_type
杂志文章abstract::It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement of phospholipase activation and the biochemical pathways participating in inotropic responsiveness remain unclear. The aim of the current study was to determine whether arachidonic acid...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.2.376
更新日期:1993-02-01 00:00:00
abstract::Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.38.6.2
更新日期:1976-06-01 00:00:00
abstract::A narrow zone of block in isolated false tendon preparations was created by perfusion of the central compartment (gap) of a three-compartment tissue bath with either an isotonic sucrose solution or a solution designed to mimic the extracellular milieu in ischemic tissue. Driven responses on the proximal side of the ga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.5.1129
更新日期:1981-11-01 00:00:00
abstract::Sixteen years ago, mutations in cardiac troponin (Tn)T and α-tropomyosin were linked to familial hypertrophic cardiomyopathy, thus transforming the disorder from a disease of the β-myosin heavy chain to a disease of the cardiac sarcomere. From the outset, studies suggested that mutations in the regulatory thin filamen...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.224170
更新日期:2011-03-18 00:00:00
abstract::The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to ele...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000027529.37429.38
更新日期:2002-07-26 00:00:00
abstract::To clarify the physiological role of calcium-activated neutral protease (CANP) in human platelets, we loaded the platelets with a Ca2+ -sensitive fluorescent dye, fura-2, and measured the degree of aggregation, cytosolic calcium ion concentration [( Ca2+]i), and proteolysis by sodium dodecyl sulfate-polyacrylamide gel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.2.407
更新日期:1989-02-01 00:00:00
abstract::-The vascular endothelial growth factor receptor Flk-1/KDR is highly expressed during development and almost disappears in adult tissues. Despite its biological relevance, little is known about the molecular mechanisms controlling its expression. In the present work, it is shown that cAMP response element binding prot...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:2000-06-23 00:00:00
abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.772
更新日期:1976-12-01 00:00:00
abstract::E1A can evoke G1 exit in cardiac myocytes and other cell types by displacing E2F transcription factors from tumor suppressor "pocket" proteins and by a less well-characterized p300-dependent pathway. Bypassing pocket proteins (through overexpression of E2F-1) reproduces the effect of inactivating pocket proteins (thro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.4.319
更新日期:1999-08-20 00:00:00
abstract:RATIONALE:Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region. OBJECTIVE:To establish the association of P...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.201418
更新日期:2009-09-11 00:00:00
abstract::Loss-of-function mutations in the human ERG1 potassium channel (hERG1) frequently underlie the long QT2 (LQT2) syndrome. The role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous, loss-of-function LQT2 syndrome mutation. The hERG N629D mutation was introduced into ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.177055
更新日期:2008-12-05 00:00:00
abstract::Bone morphogenetic protein receptor 2 (BMPR2) mutations have been linked to familial pulmonary arterial hypertension (PAH), but the molecular pathways leading to this severe pathology remain poorly characterized. We report that hypoxia, a paramount stimulus for the development of pulmonary hypertension, suppresses the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000237021.65103.24
更新日期:2006-08-04 00:00:00
abstract::A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0402.105956
更新日期:2002-03-08 00:00:00
abstract::Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000261658.12024.18
更新日期:2007-03-30 00:00:00
abstract::We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 3...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.4.390
更新日期:1977-04-01 00:00:00
abstract::We studied the effects of slow continuous hemorrhage (0.5 ml/kg per min) on measurements of arterial and left atrial pressures, and renal nerve activity in conscious dogs with all reflexes intact, or after sinoaortic baroreceptor denervation, cardiac denervation, or sinoaortic baroreceptor denervation plus vagal dener...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.5.788
更新日期:1985-11-01 00:00:00
abstract:RATIONALE:Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated. OBJECTIVE:We studied the molecular mechanism mediating the effect of GSK-3β acti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.249532
更新日期:2011-08-19 00:00:00
abstract::A potent transcriptional enhancer was previously identified upstream of the mouse renin gene. Within the enhancer is a TGACCT direct-repeat motif, required for enhancer activity, that is the consensus sequence recognized by members of the thyroid hormone subfamily of steroid hormone receptors. We previously reported t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000071355.82009.43
更新日期:2003-05-16 00:00:00
abstract::We investigated expression of the 5'-spliced isoform of smooth muscle myosin heavy chain (SM-MHC-B) in smooth muscle cells of cardiac vessels of the left ventricle of normotensive (Wistar-Kyoto) and spontaneously hypertensive rats of the stroke-prone strain by immunofluorescence microscopy. In parallel, liver and blad...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.2.204
更新日期:1998-07-27 00:00:00
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
更新日期:2009-07-17 00:00:00
abstract::Disturbances in cardiac metabolism underlie most cardiovascular diseases. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and cardiac-specific metabolism that occur across a spectrum of cardiovascular disease states. Findings from metabolomics studi...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.117.311002
更新日期:2018-04-27 00:00:00
abstract:RATIONALE:Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex proces...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315804
更新日期:2020-02-28 00:00:00
abstract::Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥ 65 years. The case mix of HF is changing over time with a growing proportion of cases presenting ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300268
更新日期:2013-08-30 00:00:00
abstract::To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1560
更新日期:1991-06-01 00:00:00
abstract:RATIONALE:Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. OBJECTIVE:To determine how mitochond...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301319
更新日期:2013-09-13 00:00:00
abstract:RATIONALE:Myosin light chain (MLC) phosphorylation determines vascular contractile status. In addition to the classic Ca²⁺-dependent MLC kinase (MLCK), another unidentified kinase(s) also contributes to MLC phosphorylation in living cells. Inhibitor κB kinase 2 (IKK2)-deficient mouse embryonic fibroblasts demonstrate a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301510
更新日期:2013-08-16 00:00:00
abstract::The role of Ca(2+)-dependent potassium channels in mediating vascular responses to activation of adenylate cyclase in vivo is not known. The goal of this study was to examine the hypothesis that dilatation of cerebral arterioles in response to activation of adenylate cyclase is mediated by activation of Ca(2+)-depende...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.6.1057
更新日期:1995-06-01 00:00:00
abstract::We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of beta-catenin. In this study we demonstrate directly that growth factors stimulate beta-catenin/T-cell factor (TCF) signaling ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000253533.65446.33
更新日期:2006-12-08 00:00:00
abstract::To study the effects of stretch on the function of rat left atrium, we recorded contraction force, calcium transients, and intracellular action potentials (APs) during stretch manipulations. The stretch of the atrium was controlled by intra-atrial pressure. The Frank-Starling behavior of the atrium was manifested as a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.11.1165
更新日期:1998-11-30 00:00:00
abstract::Recovery of postischemic function may be limited by energy synthesis by mitochondria, energy transfer via the creatine kinase reaction, or energy utilization at myofibrils. To identify the limiting step, we defined the relations among oxygen consumption, creatine kinase reaction velocity and cardiac performance in myo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.1.1
更新日期:1988-07-01 00:00:00