ArticleNature communications2015
Late Na(+) current and protracted electrical recovery are critical determinants of the aging myopathy.
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Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed.
- Reduction of the Fast Sodium Current in the Myocardium of Fish (Nothobranchius furzeri) during Aging.Bulletin of experimental biology and medicine · 2026Article
- A custom analysis of R-R interval properties reveals alterations in the brain-heart axis in experimental animals with metabolic syndrome.Heart rhythm O2 · 2026Article
- SASP-mediated cellular senescence following myocardial infarction: from spatiotemporal immune regulation to therapeutic strategies.Frontiers in immunology · 2026Review
- Acute GLP-1 Agonism Induces Arrhythmogenic Electrical Activity in Aged Mice Heart Through Impaired Cellular Na+ and Ca2+ Handlings: The Role of CK2 Hyperphosphorylation.Anatolian journal of cardiology · 2025Article
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- The cAMP/PKA signaling pathway conditions cardiac performance in experimental animals with metabolic syndrome.Journal of molecular and cellular cardiology · 2024Article
- Phosphorylation of cardiac sodium channel at Ser571 anticipates manifestations of the aging myopathy.American journal of physiology. Heart and circulatory physiology · 2024Article
- Age-related increases in cardiac excitability, refractoriness and impulse conduction favor arrhythmogenesis in male rats.Pflugers Archiv : European journal of physiology · 2023Article
- Age-dependent expression of ion channel genes in rat.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Candesartan Cilexetil Attenuates Arrhythmogenicity Following Pressure Overload in Rats via the Modulation of Cardiac Electrical and Structural Remodeling and Calcium Handling Dysfunction.Journal of the American Heart Association · 2022Article
- Article
- The common characteristics and mutual effects of heart failure and atrial fibrillation: initiation, progression, and outcome of the two aging-related heart diseases.Heart failure reviews · 2022Review
- Is heart failure with preserved ejection fraction a 'dementia' of the heart?Heart failure reviews · 2022Review
- Regulation of skeletal myogenesis in C2C12 cells through modulation of Pax7, MyoD, and myogenin via different low-frequency electromagnetic field energies.Technology and health care : official journal of the European Society for Engineering and Medicine · 2022Article
- Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging.Theranostics · 2022Article
- Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals.Frontiers in cardiovascular medicine · 2022Article
- Hypernatremia and intercalated disc edema synergistically exacerbate long-QT syndrome type 3 phenotype.American journal of physiology. Heart and circulatory physiology · 2021Article
- Review
- Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits.Oxidative medicine and cellular longevity · 2021Review
- Rhythm dynamics of the aging heart: an experimental study using conscious, restrained mice.American journal of physiology. Heart and circulatory physiology · 2020Article
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Authors and funding
23 authors.
Sergio SignoreDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Andrea SorrentinoDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Giulia BorghettiDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Antonio CannataDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Marianna MeoDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Yu ZhouDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Ramaswamy KannappanDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Francesco PasqualiniDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Heather O'MalleyDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Mark SundmanDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Nikolaos TsigkasDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Eric ZhangDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Christian ArrantoDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Chiara MangiaracinaDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Kazuya IsobeDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Brena F SenaCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Junghyun KimDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Polina GoichbergDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Matthias NahrendorfCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Lori L IsomDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Annarosa LeriDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Piero AnversaDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Marcello RotaDepartments of Anesthesia and Medicine and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Funding
Rebuilding the Failing HeartP01HL092868 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ANVERSA, PIERO · 2008 to 2013
$12.9MStem Cells and Cardiac AgingP01AG023071 · NIA · NEW YORK MEDICAL COLLEGE · PI ANVERSA, PIERO · 2004 to 2008
$9.5MRepair and Angiogenesis by Stem Cells in Human HeartR37HL081737 · NHLBI · NEW YORK MEDICAL COLLEGE · PI ANVERSA, PIERO · 2005 to 2015
$6.5MIGF-1, Gender, Heart Failure and Longevity: A Paradigm ShiftR01AG017042 · NIA · NEW YORK MEDICAL COLLEGE · PI ANVERSA, PIERO · 2000 to 2010
$5.3MStem Cells and Myocardial Aging in DogsP01AG043353 · NIA · UNIVERSITY OF ALBUQUERQUE · PI ANVERSA, PIERO · 2013 to 2015
$4.5MSUDEP Research Alliance: iPSC and Mouse Neurocardiac Models, Application 6 of 7U01NS090364 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L., PARENT, JACK M · 2014 to 2018
$3.3MStem Cells in the Developing HeartR01HL091021 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROTA, MARCELLO · 2009 to 2013
$2.4MRedefining Human Myocardial BiologyR01HL105532 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ANVERSA, PIERO, BUCHHOLZ, BRUCE A · 2011 to 2014
$2.2MImmortal DNA Strand and Cardiac Stem Cell AgingR01AG037495 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI ANVERSA, PIERO · 2011 to 2014
$2.0MTelomeric Shortening, p53 and miR-34a Condition Senescence of Cardiac ProgenitorsR01AG037490 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI LERI, ANNAROSA · 2010 to 2014
$1.7MCardiomyogenesis in the Adult HeartR01HL114346 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LERI, ANNAROSA, ROTA, MARCELLO · 2012 to 2015
$1.7MCardiac Stem Cells and AngiomyogenesisR01HL111183 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LERI, ANNAROSA · 2012 to 2015
$1.7MNHLBI NIH HHS P01 HL092868NHLBI NIH HHS R01 HL091021NHLBI NIH HHS R01 HL105532NHLBI NIH HHS R01 HL111183NHLBI NIH HHS R01 HL114346NHLBI NIH HHS R37 HL081737NIA NIH HHS P01 AG023071NIA NIH HHS P01 AG043353NIA NIH HHS R01 AG017042NIA NIH HHS R01 AG037490NIA NIH HHS R01 AG037495NIA NIH HHS R01 AG044455NINDS NIH HHS R01 NS076752NINDS NIH HHS U01 NS090364
Abstract
The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na(+) current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca(2+) cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca(2+) transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.
Indexed as
Action PotentialsAgingAnimalsCalciumCardiomyopathiesCollagenDisease Models, AnimalHeartHeart VentriclesMiceMice, KnockoutMyocardial ContractionMyocardiumMyocytes, CardiacPatch-Clamp TechniquesSarcoplasmic ReticulumCalciumCollagenScn1b protein, mouseSodiumVoltage-Gated Sodium Channel beta-1 Subunit
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.