Abstract:
:The processes of excitation-contraction coupling in cardiac myocytes require enormous amounts of energy in the form of ATP, which is produced by oxidative phosphorylation in mitochondria. Due to the constantly varying workloads of the heart, efficient matching of energy supply to demand is a requisite for proper heart function. Ca(2+) is taken up by mitochondria via the mitochondrial Ca(2+) uniporter (MCU) where it stimulates key dehydrogenases of the Krebs cycle to match regeneration of NADH to its oxidation by the respiratory chain. The kinetics of mitochondrial Ca(2+) uptake, however, remain controversial due to the low Ca(2+) sensitivity of the MCU. Here, we review the evidence for the existence of a "mitochondrial Ca(2+) microdomain", in which the close association of the sarcoplasmic reticulum (SR) to mitochondria provides "hot spots" of very high Ca(2+) concentrations in the vicinity of mitochondria, sufficient to overcome the low Ca(2+) affinity of the MCU. Mitofusins 1 and 2 play redundant roles in regulating mitochondrial dynamics by controlling fusion of mitochondria with each other. Recent work revealed a unique role for mitofusin 2 in tethering mitochondria to the sarco-/endoplasmic reticulum in various cell types, including cardiac myocytes. Disruption of SR-mitochondrial Ca(2+) cross talk in heart failure through spatial and ionic alterations may give rise to energetic deficit and oxidative stress, two factors believed to play causal roles in the progression of the disease. On the other hand, excessive mitochondrial Ca(2+) uptake can trigger programmed necrosis, substantiating the ambiguity of the close interplay between these cousin organelles in health and disease. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Dorn GW 2nd,Maack Cdoi
10.1016/j.yjmcc.2012.07.015subject
Has Abstractpub_date
2013-02-01 00:00:00pages
42-9eissn
0022-2828issn
1095-8584pii
S0022-2828(12)00263-5journal_volume
55pub_type
杂志文章,评审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::During lipid oversupply, the heart becomes insulin resistant, as exemplified by defective insulin-stimulated glucose uptake, and will develop diastolic dysfunction. In the healthy heart, not only insulin, but also increased contractile activity stimulates glucose uptake. Upon increased contraction both AMP-activated p...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.11.005
更新日期:2013-02-01 00:00:00
abstract::The adenosine A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) and bradykinin both limit infarction when administered at reperfusion in rabbits. This study compares the signal transduction pathways responsible for their anti-infarct effect. Receptor agonists were administered to isolated rabbit hearts ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.12.008
更新日期:2004-03-01 00:00:00
abstract::We made novel measurements of the influence of rest intervals and stimulation frequency on twitch contractions and on sarcoplasmic reticulum (SR) Ca(2+)-content (using rapid cooling contractures, RCCs) in isolated ventricular muscle strips from rat and rabbit hearts at a physiological temperature of 37 degrees C. In a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1252
更新日期:2000-12-01 00:00:00
abstract::We have recently shown that norepinephrine (NE) pretreatment attenuates Ca2+ overloading in cardiac rat trabeculae during metabolic inhibition (MI) with NaCN (2 mmol/l), and improves contractile recovery during a subsequent recovery period (RP). In the present study, we investigated the effects of the continuous prese...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0617
更新日期:1998-02-01 00:00:00
abstract::Peroxynitrite is a potent oxidant and nitrating species proposed as a direct effector of myocardial damage in a wide range of cardiac diseases. Whether peroxynitrite also acts indirectly, by modulating cell signal transduction pathways in the myocardium, has not been investigated. Here, we examined the ability of pero...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.02.020
更新日期:2005-05-01 00:00:00
abstract::Atrial fibrillation (AF) is commonly associated with chronic dilatation of the left atrium, both in human disease and animal models. The immediate signaling enzyme phospholipase C (PLC) is activated by mechanical stretch to generate the Ca2+-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-di...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.08.020
更新日期:2009-11-01 00:00:00
abstract::Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence sim...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1185
更新日期:1994-12-01 00:00:00
abstract::Cardioprotection and preconditioning mediated via G-protein-coupled receptors may be lost or impaired with advancing age, limiting ischemic tolerance and the ability to pharmacologically protect older hearts from ischemic injury. Our preliminary findings indicated a loss of delta-opioid receptor-mediated protection in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.02.011
更新日期:2007-05-01 00:00:00
abstract::The relationship between reperfusion-induced arrhythmias and the size of the occluded zone was examined. The isolated perfuse rat heart was used because its negligible collateral flow maximizes susceptibility to arrhythmias and reduces variability. Ischemia lasting 10 min was followed by 10 min of reperfusion. A const...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90828-6
更新日期:1989-06-01 00:00:00
abstract::Nitrovasodilators relax vascular smooth muscle by stimulating guanylate cyclase. Ignarro et al. (1981) proposed a mechanistic scheme according to which organic nitrates release nitrite in the presence of thiols. The corresponding nitrous acid would decay leading to nitric oxide, which then would react with another thi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80130-5
更新日期:1988-05-01 00:00:00
abstract::Biglycan, a small dermatan sulphate proteoglycan, has been postulated to interact with other components of the extracellular matrix (ECM), specifically collagens. We hypothesized that biglycan messenger ribonucleic acid (mRNA) is increased in the myocardial infarct zone. Biglycan mRNA expression after acute myocardial...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0737
更新日期:1998-09-01 00:00:00
abstract::Understanding the process of Ca(2+)/Mg(2+)exchange during muscle excitation and relaxation is fundamental to elucidating the mechanism of Ca(2+)-regulated muscle contraction. During the resting phase, the C-domain of cardiac troponin C may be occupied by either Ca(2+)or Mg(2+). Here, complexes of recombinant cardiac t...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1174
更新日期:2000-08-01 00:00:00
abstract::Identification of proteins that interact with Cx43 has been instrumental in the understanding of gap junction (GJ) regulation. An in vitro phosphorylation screen identified that Protein tyrosine kinase 2 beta (Pyk2) phosphorylated purified Cx43CT and this led us to characterize the impact of this phosphorylation on Cx...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.09.004
更新日期:2020-12-01 00:00:00
abstract::The kappa-opioid receptor exerts a negative modulatory action on the beta-adrenoceptor and the action is blunted in adult spontaneously hypertensive rats (SHR). In order to determine whether the blunted negative modulation of the beta-adrenoceptor by the kappa-opioid receptor contributes to the development of hyperten...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0896
更新日期:1999-03-01 00:00:00
abstract::Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80469-2
更新日期:1986-02-01 00:00:00
abstract::The BH3-only proteins, including BNip3, are members of the Bcl-2 family of cell death-regulating factors. Whereas proteins such as Bax and Bak play a central role in most forms of apoptosis, the BH3-only proteins appear to modulate apoptosis through cell type- and signal-specific pathways. This review will focus on ou...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2004.11.007
更新日期:2005-01-01 00:00:00
abstract::Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.1538
更新日期:2002-05-01 00:00:00
abstract::Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.09.007
更新日期:2015-11-01 00:00:00
abstract::Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.08.005
更新日期:2011-02-01 00:00:00
abstract::Cardiac ventricular responsiveness to serotonin appears in rat postinfarction congestive heart failure (CHF), mainly mediated by 5-HT(4) receptors in chronic dilated CHF and 5-HT(2A) receptors in acute CHF. To differentiate between the effects of left ventricular (LV) hypertrophy and failure on 5-HT(2A)- and 5-HT(4)-m...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.08.019
更新日期:2007-12-01 00:00:00
abstract::Cardiac hypertrophy is characterized, among others, by the molecular events which selectively activate the expression of genes for contractile proteins within individual myocardial cells. As such, myosin light chain 2 (MLC-2), which is upregulated in the hypertrophic state in both rat and human, serves as a marker for...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(95)92019-6
更新日期:1995-10-01 00:00:00
abstract::Cardiomyocyte progenitor cells (CMPCs) can be isolated from the human heart and differentiated into cardiomyocytes in vitro. A comprehensive assessment of their electrical phenotype upon differentiation is essential to predict potential future applications of this cell source. CMPCs isolated from human fetal heart wer...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.05.004
更新日期:2010-01-01 00:00:00
abstract::During systole, Ca2+ is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) while, simultaneously, other ions (specifically K+, Mg2+, and Cl-) provide counter-ion flux. These ions move back into the SR during diastole through the SERCA pump and SR K+ and Cl- channels. In homeostasis, all i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.10.018
更新日期:2017-02-01 00:00:00
abstract::The purpose of this study was to investigate whether vitamin D3 deficiency affects the cardiac function of chick hearts directly or whether the influence is secondary through the hormone's effect on serum calcium levels. To this end, three experimental groups were studied: (a) the control group of vitamin D3 supplemen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1010
更新日期:1993-01-01 00:00:00
abstract::Exposure to carbon monoxide (CO) during the fetal and neonatal period was used to evaluate cardiac ventricular regional weight and myocyte growth response to an increased hemodynamic load. Date-mated Sprague-Dawley rats inhaled 200 ppm CO from day 7 of pregnancy until parturition; another group of pregnant rats inhale...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80913-0
更新日期:1986-05-01 00:00:00
abstract::Atrial tachyarrhythmias, the most common type of cardiac arrhythmias, are associated with greater stroke risk. Muscarinic cholinergic agonists have been shown to facilitate atrial tachyarrhythmia maintenance in the absence of cardiac disease. This has been attributed to action potential shortening, which enhances myoc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.10.004
更新日期:2013-12-01 00:00:00
abstract::In mammalian species, including man, the duration of myocardial contraction is shorter in atria than ventricles. Total contraction time depends at least in part on phosphorylation and dephosphorylation of cardiac regulatory proteins. Dephosphorylation reactions are mediated by protein phosphatases. In the mammalian he...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1265
更新日期:2000-12-01 00:00:00
abstract::Previous studies have demonstrated that acute ethanol exposure induces activation of delta protein kinase C (deltaPKC) and epsilonPKC, and mimics ischemic preconditioning via epsilonPKC activation. However, the role of deltaPKC isozyme in ischemia and reperfusion is still controversial. Here, we investigated the role ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.05.014
更新日期:2005-08-01 00:00:00
abstract::Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed in the mammalian heart. A recent report has shown that their expression is differentially regulated during ontogenic development, but the accumulation of the two mRNA species and their concentration ratio have not been determined. We thus...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90002-0
更新日期:1995-09-01 00:00:00