5,721 results match your criteria atrial cardiomyocytes

Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.

Cardiovasc Res 2021 May 6. Epub 2021 May 6.

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, 215000, China.

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Read More

View Article and Full-Text PDF

Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel.

Nat Commun 2021 05 5;12(1):2551. Epub 2021 May 5.

Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, QC, Canada.

Endogenous cardiac pacemaker function regulates the rate and rhythm of cardiac contraction. The mutation p.Lys23Glu in the cohesin protein Shugoshin-1 causes severe heart arrhythmias due to sinoatrial node dysfunction and a debilitating gastrointestinal motility disorder, collectively termed the Chronic Atrial and Intestinal Dysrhythmia Syndrome, linking Shugoshin-1 and pacemaker activity. Read More

View Article and Full-Text PDF

[Electrophysiological Effects of Ionophore-induced Increases in Intracellular Na in Cardiomyocytes].

Yakugaku Zasshi 2021 ;141(5):705-710

Department of Rational Medicinal Science, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.

Na ionophores increase intracellular Na ([Na]i). Membrane potentials and currents were measured using microelectrode and whole-cell patch-clamp techniques. Monensin (10-3×10 M) reduced the slope of the pacemaker potentials and shortened the action potential duration (APD) in sino-atrial nodal and Purkinje cells. Read More

View Article and Full-Text PDF
January 2021

Finding a new job: glutamate signaling acts in atrial cardiomyocytes.

Cell Res 2021 May 4. Epub 2021 May 4.

Research Centre, Montreal Heart Institute and University of Montreal, Montreal, QC, Canada.

View Article and Full-Text PDF

Characterization of the HCN Interaction Partner TRIP8b/PEX5R in the Intracardiac Nervous System of TRIP8b-Deficient and Wild-Type Mice.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Division of Cardiology, EVK Düsseldorf, cNEP, Cardiac Neuro- and Electrophysiology Research Consortium, Kirchfeldstrasse 40, 40217 Düsseldorf, Germany.

The tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b/PEX5R) is an interaction partner and auxiliary subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are key for rhythm generation in the brain and in the heart. Since TRIP8b is expressed in central neurons but not in cardiomyocytes, the TRIP8b-HCN interaction has been studied intensely in the brain, but is deemed irrelevant in the cardiac conduction system. Still, to date, TRIP8b has not been studied in the intrinsic cardiac nervous system (ICNS), a neuronal network located within epicardial fat pads. Read More

View Article and Full-Text PDF

Shenxian-Shengmai Oral Liquid Improves Sinoatrial Node Dysfunction through the PKC/NOX-2 Signaling Pathway.

Evid Based Complement Alternat Med 2021 10;2021:5572140. Epub 2021 Apr 10.

Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.

Sick sinus syndrome (SSS) is one of the common causes of cardiac syncope and sudden death; the occurrence of SSS is associated with the accumulation of ROS in the sinoatrial node (SAN). Shenxian-shengmai (SXSM) is a traditional Chinese medicine available as oral liquid that causes a significant increase in heart rate. The objective of this study is to observe the improvement of SXSM on SAN function in SSS mice and explore its potential mechanism. Read More

View Article and Full-Text PDF

Cell surface markers for immunophenotyping human pluripotent stem cell-derived cardiomyocytes.

Pflugers Arch 2021 Apr 30. Epub 2021 Apr 30.

Department, of Medicine and Therapeutics, Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, HKSAR, China.

Human pluripotent stem cells (hPSC) self-renew and represent a potentially unlimited source for the production of cardiomyocytes (CMs) suitable for studies of human cardiac development, drug discovery, cardiotoxicity testing, and disease modelling and for cell-based therapies. However, most cardiac differentiation protocols yield mixed cultures of atrial-, ventricular-, and pacemaker-like cells at various stages of development, as well as non-CMs. The proportions and maturation states of these cell types result from disparities among differentiation protocols and time of cultivation, as well as hPSC reprogramming inconsistencies and genetic background variations. Read More

View Article and Full-Text PDF

Patch-Clamp Recordings of Action Potentials From Human Atrial Myocytes: Optimization Through Dynamic Clamp.

Front Pharmacol 2021 12;12:649414. Epub 2021 Apr 12.

Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Consequently, novel therapies are being developed. Ultimately, the impact of compounds on the action potential (AP) needs to be tested in freshly isolated human atrial myocytes. Read More

View Article and Full-Text PDF

Variant Intronic Enhancer Controls Expression and Heart Conduction.

Circulation 2021 Apr 29. Epub 2021 Apr 29.

Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, location AMC, Amsterdam, The Netherlands.

Genetic variants in , encoding the neural voltage-gated sodium channel NaV1.8, are strongly associated with atrial fibrillation, Brugada syndrome, cardiac conduction velocities and heart rate. The cardiac function of has not been resolved, however, and diverging mechanisms have been proposed. Read More

View Article and Full-Text PDF

Phenanthrene alters the electrical activity of atrial and ventricular myocytes of a polar fish, the Navaga cod.

Aquat Toxicol 2021 Apr 4;235:105823. Epub 2021 Apr 4.

Faculty of Biology, Medicine and Health, Core Technology Facility, University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK. Electronic address:

Oil and gas exploration in the Arctic can result in the release of polycyclic aromatic hydrocarbons (PAHs) into relatively pristine environments. Following the recent spill of approximately 17 500 tonnes of diesel fuel in Norilsk, Russia, May 2020, our study focussed on the effects of phenanthrene, a low molecular weight PAH found in diesel and crude oil, on the isolated atrial and ventricular myocytes from the heart of the polar teleost, the Navaga cod (Eleginus nawaga). Acute exposure to phenanthrene in navaga cardiomyocytes caused significant action potential (AP) prolongation, confirming the proarrhythmic effects of this pollutant. Read More

View Article and Full-Text PDF

Bioengineering approaches to mature induced pluripotent stem cell-derived atrial cardiomyocytes to model atrial fibrillation.

Exp Biol Med (Maywood) 2021 Apr 25:15353702211009146. Epub 2021 Apr 25.

Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.

Induced pluripotent stem cells (iPSCs) serve as a robust platform to model several human arrhythmia syndromes including atrial fibrillation (AF). However, the structural, molecular, functional, and electrophysiological parameters of patient-specific iPSC-derived atrial cardiomyocytes (iPSC-aCMs) do not fully recapitulate the mature phenotype of their human adult counterparts. The use of physiologically inspired microenvironmental cues, such as postnatal factors, metabolic conditioning, extracellular matrix (ECM) modulation, electrical and mechanical stimulation, co-culture with non-parenchymal cells, and 3D culture techniques can help mimic natural atrial development and induce a more mature adult phenotype in iPSC-aCMs. Read More

View Article and Full-Text PDF

An exosomal-carried short periostin isoform induces cardiomyocyte proliferation.

Theranostics 2021 23;11(12):5634-5649. Epub 2021 Mar 23.

Laboratory of Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Lugano, Switzerland.

Although a small number of cardiomyocytes may reenter the cell cycle after injury, the adult mammalian heart is incapable of a robust cardiomyocyte proliferation. Periostin, a secreted extracellular matrix protein, has been implicated as a regulator of cardiomyocyte proliferation; however, this role remains controversial. Alternative splicing of the human periostin gene results in 6 isoforms lacking sequences between exons 17 and 21, in addition to full-length periostin. Read More

View Article and Full-Text PDF

A Computational Study of the Effects of Tachycardia-Induced Remodeling on Calcium Wave Propagation in Rabbit Atrial Myocytes.

Front Physiol 2021 9;12:651428. Epub 2021 Apr 9.

Simula Research Laboratory, Computational Physiology Department, Lysaker, Norway.

In atrial cardiomyocytes without a well-developed T-tubule system, calcium diffuses from the periphery toward the center creating a centripetal wave pattern. During atrial fibrillation, rapid activation of atrial myocytes induces complex remodeling in diffusion properties that result in failure of calcium to propagate in a fully regenerative manner toward the center; a phenomenon termed "calcium silencing." This has been observed in rabbit atrial myocytes after exposure to prolonged rapid pacing. Read More

View Article and Full-Text PDF

Smyd1 Orchestrates Early Heart Development Through Positive and Negative Gene Regulation.

Front Cell Dev Biol 2021 1;9:654682. Epub 2021 Apr 1.

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China.

SET and MYND domain-containing protein 1 (Smyd1) is a striated muscle-specific histone methyltransferase. Our previous work demonstrated that deletion of Smyd1 in either cardiomyocytes or the outflow tract (OFT) resulted in embryonic lethality at E9.5, with cardiac structural defects such as truncation of the OFT and right ventricle and impaired expansion and proliferation of the second heart field (SHF). Read More

View Article and Full-Text PDF

Cues from human atrial extracellular matrix enrich the atrial differentiation of human induced pluripotent stem cell-derived cardiomyocytes.

Biomater Sci 2021 Apr 16. Epub 2021 Apr 16.

Texas Heart Institute, 6770 Bertner Avenue, MC 1-135, Houston, TX 77030, USA. and RegenMedix Consulting LLC, Houston, TX 77030, USA.

New robust and reproducible differentiation approaches are needed to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes of specific subtypes in predictable quantities for tissue-specific disease modeling, tissue engineering, and eventual clinical translation. Here, we assessed whether powdered decellularized extracellular matrix (dECM) particles contained chamber-specific cues that could direct the cardiac differentiation of human iPSCs toward an atrial phenotype. Human hearts were dissected and the left ventricle (LV) and left atria (LA) were isolated, minced, and decellularized using an adapted submersion decellularization technique to generate chamber-specific powdered dECM. Read More

View Article and Full-Text PDF

Targeting of Potassium Channels in Cardiac Arrhythmias.

Trends Pharmacol Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of Physiology & Pharmacology, Sackler Faculty of Medicine and Sagol School of Neurosciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

Cardiomyocytes are endowed with a complex repertoire of ion channels, responsible for the generation of action potentials (APs), travelling waves of electrical excitation, propagating throughout the heart and leading to cardiac contractions. Cardiac AP waveforms are shaped by a striking diversity of K channels. The pivotal role of K channels in cardiac health and disease is underscored by the dramatic impact that K channel dysfunction has on cardiac arrhythmias. Read More

View Article and Full-Text PDF

Cardiac potassium inward rectifier Kir2: Review of structure, regulation, pharmacology, and arrhythmogenesis.

Heart Rhythm 2021 Apr 20. Epub 2021 Apr 20.

Cellular and Molecular Arrhythmia Research Program, Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin. Electronic address:

Potassium inward rectifier channel Kir2 is an important component of terminal cardiac repolarization and resting membrane stability. This functionality is part of balanced cardiac excitability and is a defining feature of excitable cardiac membranes. "Gain-of-function" or "loss-of-function" mutations in KCNJ2, the gene encoding Kir2. Read More

View Article and Full-Text PDF

Attenuated β-adrenergic response in calcium/calmodulin-dependent protein kinase IV-knockout mice.

PLoS One 2021 15;16(4):e0249932. Epub 2021 Apr 15.

Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.

In the present study, we examined the importance of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) in the regulation of cardiac function using genetically modified CaMKIV-null mice. RT-PCR analysis revealed decreased expression of voltage-dependent calcium channels in the cardiac myocytes of CaMKIV-null mice compared with wild-type mice. CaMKIV-null mice showed shortened QT time on electrocardiograms. Read More

View Article and Full-Text PDF

Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans.

Basic Res Cardiol 2021 Apr 12;116(1):24. Epub 2021 Apr 12.

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond Street, 4032, Debrecen, Hungary.

Omecamtiv mecarbil (OM) is a promising novel drug for improving cardiac contractility. We tested the therapeutic range of OM and identified previously unrecognized side effects. The Ca sensitivity of isometric force production (pCa) and force at low Ca levels increased with OM concentration in human permeabilized cardiomyocytes. Read More

View Article and Full-Text PDF

Local Action of Neprilysin Exacerbates Pressure Overload Induced Cardiac Remodeling.

Hypertension 2021 Apr 12:HYPERTENSIONAHA12016445. Epub 2021 Apr 12.

Cardiovascular Medicine, Nara Medical University, Nara, Japan (H.N., T.K., K.O., Y.N., T. Nakano, S.I., T.U., A.S., T. Nishida, T.S., S.O., M.W., R.K., Y.S.).

NEP (Neprilysin) degrades natriuretic peptides, and its inhibition is a clinically accepted target for heart failure treatment. NEP is widely expressed in various organs, including the heart. However, the pathophysiological significance of local cardiac NEP is not fully understood. Read More

View Article and Full-Text PDF

Ligand-activated RXFP1 gene therapy ameliorates pressure overload-induced cardiac dysfunction.

Mol Ther 2021 Apr 9. Epub 2021 Apr 9.

Department of Internal Medicine III, Cardiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Germany. Electronic address:

Recurrent episodes of decompensated heart failure (HF) represent an emerging cause of hospitalizations in developed countries with an urgent need for effective therapies. Recently, the pregnancy-related hormone relaxin (RLN) was found to mediate cardio-protective effects and act as a positive inotrope in the cardiovascular system. RLN binds to the RLN family peptide receptor 1 (RXFP1), which is predominantly expressed in atrial cardiomyocytes. Read More

View Article and Full-Text PDF

Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes.

Cell Res 2021 Apr 6. Epub 2021 Apr 6.

Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. Read More

View Article and Full-Text PDF

Cardiovascular effects of metoclopramide and domperidone on human 5-HT-serotonin-receptors in transgenic mice and in human atrial preparations.

Eur J Pharmacol 2021 Mar 31;901:174074. Epub 2021 Mar 31.

Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, D-06097, Halle, Germany. Electronic address:

It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT-receptors. Therefore, we studied transgenic mice that only express the human 5-HT receptor in cardiomyocytes in the atrium and in the ventricle (5-HT-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC = 6. Read More

View Article and Full-Text PDF

Deletion of Alters the Function of the Na1.5 Channel in Murine Cardiac Myocytes.

Int J Mol Sci 2021 Mar 26;22(7). Epub 2021 Mar 26.

Institute of Biochemistry and Molecular Medicine, and Swiss National Centre of Competence in Research (NCCR) TransCure, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.

Transient receptor potential melastatin member 4 (TRPM4) encodes a Ca-activated, non-selective cation channel that is functionally expressed in several tissues, including the heart. Pathogenic mutants in have been reported in patients with inherited cardiac diseases, including conduction blockage and Brugada syndrome. Heterologous expression of mutant channels in cell lines indicates that these mutations can lead to an increase or decrease in TRPM4 expression and function at the cell surface. Read More

View Article and Full-Text PDF

Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong 2500, Australia.

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. Read More

View Article and Full-Text PDF

Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Division of Cardiology, Department of Internal Medicine, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.

By promoting atrial structural remodeling, atrial hypoxia contributes to the development of the atrial fibrillation substrate. Our study aimed to investigate the modulatory effect of hypoxia on profibrotic activity in cultured HL-1 cardiomyocytes and explore the possible signaling transduction mechanisms of profibrotic activity in vitro. Hypoxia (1% O) significantly and time-dependently increased the expression of hypoxia-inducible factor (HIF)-1α and fibrotic marker proteins collagen I and III (COL1A and COL3A), transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). Read More

View Article and Full-Text PDF

Disease Modeling and Disease Gene Discovery in Cardiomyopathies: A Molecular Study of Induced Pluripotent Stem Cell Generated Cardiomyocytes.

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.

The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The generated CMs expressed CM-specific genes and were highly concordant in their total expressed transcriptome across the 12 samples (correlation coefficient at 95% CI =0. Read More

View Article and Full-Text PDF

Extracellular Vesicles from Epicardial Fat Facilitate Atrial Fibrillation.

Circulation 2021 Apr 1. Epub 2021 Apr 1.

Neufeld and Tamman Cardiovascular Research Institutes, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Israel; Heart Center, Sheba Medical Center, Tel Hashomer, Israel.

The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. Read More

View Article and Full-Text PDF

Increased ROS-Mediated CaMKII Activation Contributes to Calcium Handling Abnormalities and Impaired Contraction in Barth Syndrome.

Circulation 2021 Apr 1. Epub 2021 Apr 1.

Department of Cardiology, Boston Children's Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA.

Mutations in tafazzin (), a gene required for biogenesis of cardiolipin, the signature phospholipid of the inner mitochondrial membrane, causes Barth syndrome (BTHS). Cardiomyopathy and risk of sudden cardiac death are prominent features of BTHS, but the mechanisms by which impaired cardiolipin biogenesis causes cardiac muscle weakness and arrhythmia are poorly understood. We performed in vivo electrophysiology to define arrhythmia vulnerability in cardiac specific knockout mice. Read More

View Article and Full-Text PDF

Influence of sex on intracellular calcium homeostasis in patients with atrial fibrillation.

Cardiovasc Res 2021 Mar 31. Epub 2021 Mar 31.

Biomedical Research Institute Barcelona Centre IIBB-CSIC.

Aims: Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue.

Methods And Results: Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (ICa) density was significantly smaller in males with than without AF (-1. Read More

View Article and Full-Text PDF