Inherited Dysfunction of Sarcoplasmic Reticulum Ca ²⁺ Handling and Arrhythmogenesis

Circulation Research, Journal Year: 2011, Volume and Issue: 108(7), P. 871 - 883

Published: March 31, 2011

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease occurring in patients with a structurally normal heart: the characterized by life-threatening arrhythmias elicited stress and emotion. In 2001, ryanodine receptor was identified as gene that linked to CPVT; shortly thereafter, cardiac calsequestrin implicated recessive form of same disease. It became clear abnormalities intracellular Ca(2+) regulation could profoundly disrupt electrophysiological properties heart. this article, we discuss molecular basis pathophysiological mechanisms are impacting clinical diagnosis management affected individuals. As today, interaction between basic scientists clinicians understand CPVT identify new therapeutic strategies one most compelling examples importance translational research cardiology.

Language: Английский

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Human Engineered Heart Tissue: Analysis of Contractile Force

Stem Cell Reports, Journal Year: 2016, Volume and Issue: 7(1), P. 29 - 42

Published: May 21, 2016

Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established human induced pluripotent stem cell-derived (hiPSC-CM). This study describes generation 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM their physiological pharmacological properties. CM were differentiated hiPSC by a growth factor-based three-stage protocol. EHTs generated analyzed histologically functionally. HiPSC-CM showed well-developed sarcomeric organization alignment, frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that replicated canonical response to regulators inotropy, membrane- calcium-clock mediators pacemaking, modulators ion-channel currents, proarrhythmic compounds with unprecedented precision. The demonstrates high degree similarity between EHT format native tissue, indicating are useful for preclinical drug testing disease modeling.

Language: Английский

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Loss of Cav1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness

Nature Neuroscience, Journal Year: 2010, Volume and Issue: 14(1), P. 77 - 84

Published: Dec. 5, 2010

Language: Английский

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Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18

Nature Biotechnology, Journal Year: 2012, Volume and Issue: 31(1), P. 54 - 62

Published: Dec. 16, 2012

Language: Английский

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Biophysical Characterization of the Underappreciated and Important Relationship Between Heart Rate Variability and Heart Rate

Hypertension, Journal Year: 2014, Volume and Issue: 64(6), P. 1334 - 1343

Published: Sept. 16, 2014

Heart rate (HR) variability (HRV; beat-to-beat changes in the R-wave to interval) has attracted considerable attention during past 30+ years (PubMed currently lists >17 000 publications). Clinically, a decrease HRV is correlated higher morbidity and mortality diverse conditions, from heart disease fetal distress. It usually attributed fluctuation cardiac autonomic nerve activity. We calculated parameters variety of preparations (including humans, living animals, Langendorff-perfused heart, single sinoatrial nodal cell) species, combining this with data previously published articles. show that regardless there universal exponential decay-like relationship between HR. Using 2 biophysical models, we develop theory for confirm primarily dependent on HR cannot be used any simple way assess activity heart. suggest correlation change altered substantially attributable concurrent This calls re-evaluation findings many articles have not adjusted properly or at all differences when comparing multiple circumstances.

Language: Английский

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Calmodulin-Dependent Protein Kinase II: Linking Heart Failure and Arrhythmias

Circulation Research, Journal Year: 2012, Volume and Issue: 110(12), P. 1661 - 1677

Published: June 7, 2012

Understanding relationships between heart failure and arrhythmias, important causes of suffering sudden death, remains an unmet goal for biomedical researchers physicians. Evidence assembled over the past decade supports a view that activation multifunctional Ca 2+ calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction cell membrane electrical instability. CaMKII follows increases in intracellular or oxidation, upstream signals with capacity to transition into calmodulin-independent constitutively active enzyme. Constitutively appears poised participate disease pathways by catalyzing phosphorylation classes targets excitation–contraction coupling survival, including ion channels homeostatic proteins, transcription factors drive hypertrophic inflammatory gene expression. This rich diversity downstream helps explain potential simultaneously affect mechanical properties muscle cells. Proof-of-concept studies from growing number investigators show inhibition is beneficial improving performance reducing arrhythmias. We review molecular physiology discuss actions at key cellular results animal models hypertrophy, dysfunction, arrhythmias suggest may benefit function while

Language: Английский

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Nonlinear and stochastic dynamics in the heart

Physics Reports, Journal Year: 2014, Volume and Issue: 543(2), P. 61 - 162

Published: May 22, 2014

Language: Английский

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The autonomic nervous system and cardiac arrhythmias: current concepts and emerging therapies

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: 16(12), P. 707 - 726

Published: June 13, 2019

Language: Английский

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The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias

Nature Medicine, Journal Year: 2014, Volume and Issue: 20(2), P. 184 - 192

Published: Jan. 19, 2014

Language: Английский

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Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(4), P. 396 - 414.e9

Published: April 1, 2023

Language: Английский

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