Abstract:
:Regional depolarization of the mitochondrial network can alter cellular electrical excitability and increase the propensity for reentry, in part, through the opening of sarcolemmal KATP channels. Mitochondrial inner membrane potential (ΔΨm) instability or oscillation can be induced in myocytes by exposure to reactive oxygen species (ROS), laser excitation, or glutathione depletion, and is thought to be a major factor in arrhythmogenesis during ischemia-reperfusion. Nevertheless, the correlation between ΔΨm recovery kinetics and reperfusion-induced arrhythmias has been difficult to demonstrate experimentally. Here, we investigate the relationship between subcellular changes in ΔΨm, cellular glutathione redox potential, electrical excitability, and wave propagation during coverslip-induced ischemia-reperfusion (IR) in neonatal rat ventricular myocyte (NRVM) monolayers. Ischemia led to decreased action potential amplitude and duration followed by electrical inexcitability after ~15min of ischemia. ΔΨm depolarization occurred in two phases during ischemia: in phase 1 (<30min ischemia), mitochondrial clusters within individual NRVMs depolarized, while phase 2 ΔΨm depolarization (30-60min) was characterized by global functional collapse of the mitochondrial network across the whole ischemic region of the monolayer, typically involving a propagating metabolic wave. Oxidation of the glutathione (GSSG:GSH) redox potential occurred during ischemia, followed by recovery upon reperfusion (i.e., lifting the coverslip). ΔΨm recovered in the mitochondria of individual myocytes quite rapidly upon reperfusion (<5min), but was highly unstable, characterized by subcellular oscillations or flickering of clusters of mitochondria in NRVMs across the reperfused region. Electrical excitability also recovered in a heterogeneous manner, providing an arrhythmogenic substrate which led to formation of sustained reentry. Treatment with 4'-chlorodiazepam, a peripheral benzodiazepine receptor ligand, prevented ΔΨm oscillation, improved GSH recovery rate, and prevented reentry during reperfusion, indicating that stabilization of mitochondrial network dynamics is important for preventing post-ischemic arrhythmias. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Solhjoo S,O'Rourke Bdoi
10.1016/j.yjmcc.2014.09.024subject
Has Abstractpub_date
2015-01-01 00:00:00pages
90-9eissn
0022-2828issn
1095-8584pii
S0022-2828(14)00305-8journal_volume
78pub_type
杂志文章abstract::PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.09.124
更新日期:2008-12-01 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::Cardiac myocytes in rat hearts lose their ability to undergo cytokinesis between day 3 and day 4, resulting in the formation of binucleated myocytes. Failure in the formation of the actin-myosin contractile ring could cause cardiac myocytes to be defective in cytokinesis. Enzymatically isolated cardiac myocytes from 2...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0381
更新日期:1997-06-01 00:00:00
abstract::Human vascular connexins (Cx37, Cx40, Cx43, and Cx45) can form various types of gap junction channels to synchronize vasodilation/constriction to control local circulation. Most of our knowledge on heterotypic gap junctions of these vascular connexins was from studies on rodent connexins. In human vasculature, the sam...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.013
更新日期:2019-02-01 00:00:00
abstract::Cardiac calcium channel activity is markedly increased by beta-adrenergic agents or calcium agonists such as Bay K 8644. The molecular mechanisms underlying these important modulatory effects have been studied with patch clamp techniques by several groups. This paper presents new experiments and reviews published evid...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(86)80941-5
更新日期:1986-07-01 00:00:00
abstract::Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidase (MAO) has been described as a prominent source. MAOs are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generat...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2013.12.032
更新日期:2014-08-01 00:00:00
abstract::Understanding the inflammatory response to myocardial ischemia is an important part of achieving the elusive clinical goal of perfect myocardial protection. While it is established that estrogen affects the chronic inflammatory processes of coronary atherosclerosis, the effects of estrogen on acute myocardial proinfla...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.06.019
更新日期:2006-02-01 00:00:00
abstract::Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.09.009
更新日期:2018-11-01 00:00:00
abstract::Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing o...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.05.004
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.07.004
更新日期:2020-09-01 00:00:00
abstract::Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity. We found that Cx40/Cx45 double deficiency (Cx40(-/-)/Cx45(+/-)) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth. The majority of Cx40(-/-)/C...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.07.005
更新日期:2006-11-01 00:00:00
abstract::Triamterene (TA) inhibits in the microM range, as was previously shown in our laboratory, the positive inotropic action of beta-adrenoceptor agonists like isoproterenol in atrial preparations, when applied first. This interaction may be best explained by a direct influence of TA on the beta-adrenergic receptor-site it...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)91343-3
更新日期:1983-05-01 00:00:00
abstract::The effects of Cobra venom cardiotoxin (CTX) on the cellular morphology, twitch amplitude and intracellular calcium ([Ca2+]i) of the ventricular myocytes were studied. [Ca2+]i and twitch amplitude were determined with a fluorometric ratio method using Fura-2/AM and Calcium Green-1 as calcium indicators, and a videomic...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0511
更新日期:1997-10-01 00:00:00
abstract::Recent work has highlighted the role of NR4A receptors in atherosclerosis and inflammation. In vascular smooth muscle cell (VSMC) proliferation, however, NOR-1 (neuron-derived orphan receptor-1) exerts antagonistic effects to Nur77 and Nurr1. The aim of this study was to analyse the effect of NOR-1 in VSMC inflammator...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.12.015
更新日期:2015-03-01 00:00:00
abstract::The objective of this study was to characterize the effect of prostacyclin (PGI2) on ventricular function following total global ischemia in isolated working rat hearts and to investigate the mechanism of its action. Ischemia was initiated for 10, 15, 20 or 25 min with or without treatment with PGI2. Increasing durati...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90749-9
更新日期:1989-03-01 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: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::Chemokines are small molecular weight proteins that play important roles in inflammation. Originally described as chemotactic cytokines, chemokines stimulate the influx of leukocytes into specific tissue compartments. These molecules also modulate gene expression in both infiltrating and resident cells to mediate a va...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1503
更新日期:2002-02-01 00:00:00
abstract::Heat shock protein 70 (HSP70) has been shown to play a fundamental role in the induction of thermotolerance in many biological systems. Elevated synthesis of HSP70 in response to diverse stresses such as heat, anoxia, ischaemia, ethanol and heavy metals has been correlated with protection against subsequent more sever...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1084
更新日期:1994-06-01 00:00:00
abstract::The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.05.014
更新日期:2020-07-01 00:00:00
abstract::Forces associated with blood flow are crucial not only for blood vessel development but also for regulation of vascular pathology. Although there have been many studies characterizing the responses to mechanical stimuli, molecular mechanisms linking biological responses to mechanical forces remain unclear. Hic-5 (hydr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.09.024
更新日期:2011-01-01 00:00:00
abstract::The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 31...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80433-3
更新日期:1986-12-01 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::There is currently a growing global burden of valvular heart diseases due to aging populations and changing lifestyles. Valvular heart diseases mainly include the malfunctioning of aortic and mitral valves and are characterized by extensive tissue remodeling, which includes calcification, endothelial dysfunction, and ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2020.03.015
更新日期:2020-05-01 00:00:00
abstract::Diabetes and hypertension both produce myocardial dysfunction that accelerates cardiovascular morbidity and mortality. Coexistence of the two often results in a more severe cardiomyopathy than either process alone. The purpose of this study was to characterize the contractile function of diabetic hypertensive cardiomy...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1431
更新日期:2001-09-01 00:00:00
abstract::Myocytes were isolated by Langendorff perfusion of rat or rabbit hearts with low calcium solution followed by collagenase and hyaluronidase, or by incubation of chunks of rat ventricular tissue in similar media. Cells were then placed in a bath on a microscope stage, superfused and electrically stimulated. Contraction...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80121-4
更新日期:1988-07-01 00:00:00
abstract::Selective pharmacological treatments targeting reperfusion injury produced modest protective effects and might be associated with immunosuppression. In order to identify novel and better-tolerated approaches, we focused on the neutralization of receptor activator of nuclear factor kappa-B ligand [RANKL], a cytokine re...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.03.013
更新日期:2016-05-01 00:00:00
abstract::To demonstrate a direct protective effect of propofol on myocardial contractile performance during an ischemic episode and investigate underlying mechanisms, isolated adult rat ventricular cardiomyocytes were subjected for 2 h to (i) ischemic medium containing 2-deoxyglucose (20 mM), gassed with 100% N(2) at pH 6.4, (...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.12.002
更新日期:2007-03-01 00:00:00
abstract::The mechanism by which Na+-H+ exchange (NHE) inhibition results in attenuation and reversal of postinfarction remodelling and heart failure remains controversial. In this study, we investigated the possible contribution of mitochondrial involvement by determining the effect of the NHE-1-specific inhibitor EMD-87580 (E...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.10.007
更新日期:2005-01-01 00:00:00
abstract::Acute adriamycin cardiotoxicity was studied in the isolated, perfused rat heart by 31P and 13C NMR spectroscopy at flow rates of 15 and 5 ml/min. Treated hearts received a total dose of 13.5 mg of adriamycin. 31P NMR spectra were collected at the beginning and end of each experiment, and cardiac function was recorded ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90082-d
更新日期:1990-10-01 00:00:00