Remodeling of cardiac t-tubules in normal and pathophysiological conditions is an important process contributing to the functional performance of the heart. While it is well documented that deterioration of t-tubule network associated with various pathological conditions can be reversed under certain conditions, the mechanistic understanding of the recovery process is essentially lacking. Accordingly, in this study we investigated some aspects of the recovery of t-tubules after experimentally-induced detubulation. T-tubules of isolated mouse ventricular myocytes were first sealed using osmotic shock approach, and their recovery under various experimental conditions was then characterized using electrophysiologic and imaging techniques. The data show that t-tubule recovery is a strongly temperature-dependent process involving reopening of previously collapsed t-tubular segments. T-tubule recovery is slowed by (1) metabolic inhibition of cells, (2) reducing influx of extracellular Ca as well as by (3) both stabilization and disruption of microtubules. Overall, the data show that t-tubule recovery is a highly dynamic process involving several central intracellular structures and processes and lay the basis for more detailed investigations in this area.
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http://dx.doi.org/10.14814/phy2.15779 | DOI Listing |
Can J Cardiol
December 2024
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Hangzhou, China; Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Hangzhou, China; School of Medicine, Shaoxing University, China. Electronic address:
In cardiomyocytes, transverse tubules (T-tubules) are sarcolemmal invaginations that facilitate excitation-contraction coupling and diastolic function. The clinical significance of T-tubules has become evident in that their remodelling is recognised as a hallmark feature of heart failure (HF) and a key contributor to disrupted Ca homeostasis, compromised cardiac function, and arrhythmogenesis. Further investigations have revealed that T-tubule remodelling is particularly pronounced in HF with reduced ejection fraction (HFrEF), but not in HF with preserved ejection fraction, implying that T-tubule remodelling may play a crucial pathophysiologic role in HFrEF.
View Article and Find Full Text PDFCirc Res
September 2024
Unit of Cardiac Physiology, Manchester Academic Health Science Centre, University of Manchester, United Kingdom.
Background: Transverse (t)-tubules drive the rapid and synchronous Ca rise in cardiac myocytes. The virtual complete atrial t-tubule loss in heart failure (HF) decreases Ca release. It is unknown if or how atrial t-tubules can be restored and how this affects systolic Ca.
View Article and Find Full Text PDFPhysiol Rep
August 2023
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Remodeling of cardiac t-tubules in normal and pathophysiological conditions is an important process contributing to the functional performance of the heart. While it is well documented that deterioration of t-tubule network associated with various pathological conditions can be reversed under certain conditions, the mechanistic understanding of the recovery process is essentially lacking. Accordingly, in this study we investigated some aspects of the recovery of t-tubules after experimentally-induced detubulation.
View Article and Find Full Text PDFNeuromuscul Disord
April 2022
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom; Department of Neurology and Clinical Neurophysiology, Guy's & St Thomas' NHS Foundation Trust and Institute of Psychiatry, Psychology & Neuroscience, Division of Neuroscience, King's College London, United Kingdom.
Mouse models of skeletal muscle channelopathies are not phenocopies of human disease. In some cases (e.g.
View Article and Find Full Text PDFFront Cardiovasc Med
January 2021
Institute of Cellular and Molecular Physiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Chronic heart failure (HF) in adults causes remodeling of the cardiomyocyte transverse tubular system (t-system), which contributes to disease progression by impairing excitation-contraction (EC) coupling. However, it is unknown if t-system remodeling occurs in pediatric heart failure. This study investigated the t-system in pediatric viral myocarditis.
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