Abstract:
:The sodium/potassium ATPase (NKA) is essential for establishing the normal intracellular [Na+] and [K+] and transmembrane gradients that are essential for many cellular functions, including cardiac electrophysiology and contractility. Different NKA isoforms exhibit differential expression levels, cellular localization, and function in different tissues and species. Prior work has indicated that the NKA-α1 isoform is quantitatively predominant in cardiac myocytes, but that the α2 isoform is preferentially concentrated in the transverse tubules (TT), possibly at junctions with the sarcoplasmic reticulum (SR) where α2 may preferentially modulate cardiac contractility. Here we measured subcellular localization of NKA-α1 and α2 using super-resolution microscopy (STED and STORM) and isoform-selective antibodies in mouse ventricular myocytes. We confirm the preferential localization of NKA-α2 in TT vs. surface sarcolemma, but also show that α2 is relatively excluded from longitudinal TT elements. In contrast NKA-α1 is relatively uniformly expressed in all three sarcolemmal regions. We also tested the hypothesis that NKA-α2 (vs. α1) is preferentially concentrated at SR junctional sites near ryanodine receptors (RyR2). The results refute this hypothesis, in that NKA-α1 and α2 were equally close to RyR2 at the TT, with no preferential NKA isoform localization near RyR2. We conclude that in contrast to relatively uniform NKA-α1 distribution, NKA-α2 is preferentially concentrated in the truly transverse (and not longitudinal) TT elements. However, NKA-α2 does not preferentially cluster at RyR2 junctions, so the TT NKA-α2 concentration may suffice for preferential effects of NKA-α2 inhibition on cardiac contractility.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Yuen GK,Galice S,Bers DMdoi
10.1016/j.yjmcc.2017.05.013subject
Has Abstractpub_date
2017-07-01 00:00:00pages
158-169eissn
0022-2828issn
1095-8584pii
S0022-2828(17)30110-4journal_volume
108pub_type
杂志文章abstract::Brugada syndrome predisposes to sudden death due to disruption of normal cardiac ion channel function, yet our understanding of the underlying cellular mechanisms is incomplete. Commonly used heterologous expression models lack many characteristics of native cardiomyocytes and, in particular, the individual genetic ba...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.10.002
更新日期:2018-01-01 00:00:00
abstract::Sensitive to apoptosis gene (SAG) is a novel RING finger protein that has been shown to be involved in protection against apoptotic cell death induced by oxidative stress in various cell types. As SAG has been previously shown to be expressed in the heart, we assessed its role in cardiac myocytes exposed to ischaemic ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(03)00003-8
更新日期:2003-03-01 00:00:00
abstract::In the mouse, genetic reduction in the Na(+), K(+)-ATPase alpha1 or alpha2 isoforms results in different functional phenotypes: heterozygous alpha2 isolated hearts are hypercontractile, whereas heterozygous alpha1 hearts are hypocontractile. We examined Na(+)/Ca(2+) exchange (NCX) currents in voltage clamped myocytes ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.03.023
更新日期:2005-07-01 00:00:00
abstract::Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) induce platelet aggregation and are potent vasoconstrictors, and they have been implicated in coronary vasospasm and myocardial infarction. The TXA2 mimetic [1S-(1 alpha, 2 beta (5Z), 3 alpha (1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1109
更新日期:1994-07-01 00:00:00
abstract::This study examined the significance of macrophage autophagy in extracellular matrix metalloproteinase inducer (EMMPRIN)-mediated atherosclerosis (AS). Apolipoprotein E-deficient (ApoE-/-) mice were fed a western diet to establish an AS model. EMMPRIN and p62/Sequestosome-1(SQSTM1) expression were evaluated in plaque ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.11.008
更新日期:2018-01-01 00:00:00
abstract::Recent improvements in survival from AIDS have been accompanied by an increased recognition of the potential importance of other manifestations of HIV infection, including cardiomyopathy. Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. We previous...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.10.006
更新日期:2006-01-01 00:00:00
abstract::We measured myosin crossbridge detachment rate and the rates of MgADP release and MgATP binding in mouse and rat myocardial strips bearing one of the two cardiac myosin heavy chain (MyHC) isoforms. Mice and rats were fed an iodine-deficient, propylthiouracil diet resulting in ~100% expression of β-MyHC in the ventricl...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.10.010
更新日期:2013-01-01 00:00:00
abstract::Cardiomyopathy of the Syrian hamster is characterized by myocardial calcium overload and focal myocardial necrosis. The cause of the myocardial calcium overload is not yet fully understood. In this study, the ultrastructural localization of calcium was determined in normal hamster hearts and in non-necrotic and necrot...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80019-1
更新日期:1988-08-01 00:00:00
abstract::The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80009-8
更新日期:1986-09-01 00:00:00
abstract::We have identified in soluble extracts of rat heart, a 500 000 dalton sulfhydryl-dependent protease which degrades globin and casein to acid-soluble peptides at an alkaline pH optimum. This enzyme was purified more than 1700-fold with respect to the postmicrosomal supernatant. On the basis of various catalytic and bio...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90304-8
更新日期:1983-01-01 00:00:00
abstract::Despite advances in the treatment of acute tissue ischemia significant challenges remain in effective cytoprotection from ischemic cell death. It has been documented that injected stem cells, such as mesenchymal stem cells (MSCs), can confer protection to ischemic tissue through the release of paracrine factors. The s...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.11.010
更新日期:2014-01-01 00:00:00
abstract::Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (DeltaG approximately (ATP)), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice ov...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.029
更新日期:2010-04-01 00:00:00
abstract::The heart contains many cell types; mechanical work is done by cardiomyocytes which do not divide but are terminally differentiated and capable of continuous protein synthesis and degradation. The steps in protein synthesis are (1) transport of amino acids into heart cells by a variety of cell-membrane carriers, (2) A...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(84)80711-7
更新日期:1984-01-01 00:00:00
abstract::Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80716-6
更新日期:1984-01-01 00:00:00
abstract::Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.05.011
更新日期:2006-08-01 00:00:00
abstract::The resting potential of "sodium-loaded' cardiac cells can transiently hyperpolarize to levels negative to the steady state resting potential [3,5,6]. Hyperpolarization is associated with the coupled efflux of Na+ and influx of K+ driven by an active transport process and may result from an increased K+ equilibrium po...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80660-4
更新日期:1984-08-01 00:00:00
abstract::Ca(2+) overload and free-radical injury are two mutually non-exclusive phenomena suggested to cause myocardial ischemia-reperfusion (IR)-induced contractile dysfunction; however, the mechanisms underlying their effects are not clear. One possible mechanism is the proteolytic modification of proteins by Ca(2+)-dependen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.04.009
更新日期:2004-07-01 00:00:00
abstract::Effects of ischemia time and treatment interventions upon troponin I (TnI) proteolysis and function of reperfused myocardium were examined in isolated, perfused rabbit hearts. Hearts were randomized to 90 min aerobic perfusion, 15 min low-flow (1 ml/min) ischemia (I) and 60 min reperfusion (R) or 60 min low-flow I and...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.1522
更新日期:2002-04-01 00:00:00
abstract::The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrh...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2015.02.013
更新日期:2015-05-01 00:00:00
abstract::Peroxynitrite and hydroxyl radical are reactive oxidants produced during myocardial reperfusion injury. In various cell types, including macrophages and smooth muscle cells, peroxynitrite and hydrogen peroxide cause DNA single strand breakage, which triggers the activation of the nuclear enzyme poly (ADP-ribose) synth...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0496
更新日期:1997-09-01 00:00:00
abstract::The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic pep...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.0985
更新日期:1999-08-01 00:00:00
abstract::Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(08)80009-0
更新日期:1995-01-01 00:00:00
abstract::Cardiac disease is frequently associated with abnormalities in electrical function that can severely impair cardiac performance with potentially fatal consequences. The available therapeutic options have some efficacy but are far from perfect. The curative potential of gene therapy makes it an attractive approach for ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.07.022
更新日期:2011-05-01 00:00:00
abstract::Adiponectin (APN), a recently discovered adipocytokine, is present in human serum in a full length (fAPN) and a globular form (gAPN). gAPN is a proteolytic cleavage product of fAPN and seems to show independent biological activities compared to the properties of fAPN. The influence of gAPN and fAPN on procoagulability...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.10.018
更新日期:2008-02-01 00:00:00
abstract::The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.08.009
更新日期:2014-11-01 00:00:00
abstract::The topic of this review is the lipidic part of the sarcolemma, the plasma membrane of the myocardial cell, and its role in (dis)function of the cardiomyocyte. First the isolation of the sarcolemma and its lipid composition are discussed. These phospholipids are not randomly distributed over the two monolayers of the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/0022-2828(95)90080-2
更新日期:1995-02-01 00:00:00
abstract:OBJECTIVE:The function of the C-terminus region of the human ether-a-go-go related gene (HERG) has not been well characterized except for its involvement in trafficking. To understand further the role of C-terminus region, we performed a functional analysis of a novel frameshift mutation (1122fs/147) identified in a Ja...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.09.010
更新日期:2004-12-01 00:00:00
abstract::Our previous work showed that myosin phosphorylation decreased the ATPase activity of skeletal muscle myofibrils that were lightly fixed with glutaraldehyde. The fixation process prevented sarcomere shortening and destruction of the ordered filament array upon the addition of ATP. We have now extended these results to...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80624-0
更新日期:1984-07-01 00:00:00
abstract::The mitral valve is a complex multilayered structure populated by fibroblast-like cells, valvular interstitial cells (VIC) which are embedded in an extracellular matrix (ECM) scaffold and are submitted to the mechanical deformations affecting valve at each heartbeat, for an average of 40 million times per year. Myxoma...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.08.008
更新日期:2019-10-01 00:00:00
abstract::The leading cause of genetic dilated cardiomyopathy (DCM) is due to mutations in the TTN gene, impacting approximately 15-20% of familial and 18% of sporadic DCM cases. Currently, there is potential for a personalized RNA-based therapeutic approach in titin-based DCM, utilizing antisense oligonucleotide (AON) mediated...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.04.014
更新日期:2019-06-01 00:00:00