Roles of phosphorylation of myosin binding protein‐C and troponin I in mouse cardiac muscle twitch dynamics

Tong, Carl W.; Gaffin, Robert D.; Zawieja, David C.; Muthuchamy, Mariappan

doi:10.1113/jphysiol.2004.062539

Cited by 76 publications

(104 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These preparations have also been shown to propagate electrical impulse and produce calcium transients that are very representative of what is measured in traditional intact and whole heart preparations [125,138]. However, a key disadvantage to using ECT preparations to study mechanics is that they still produce comparatively low active tension values, generally less than 1 mN/mm 2 [136], whereas trabeculae and papillary muscles easily produce in excess of 20 mN/mm 2 [139,140]. These low active tension values raise some questions regarding how closely these preparations mimic healthy intact tissue.…”

Section: The Need For Multicellular Tissue-scale Experimentsmentioning

confidence: 99%

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Pfeiffer

Tangney

Omens

et al. 2014

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation-contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation-contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.

show abstract

Section: The Need For Multicellular Tissue-scale Experimentsmentioning

confidence: 99%

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Pfeiffer

Tangney

Omens

et al. 2014

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

show abstract

“…GSH was determined with 50 M monochlorobimane (MCB), a membrane-permeant indicator of GSH (2). Trabeculae were loaded with 7 M CM-H 2-DCFDA and 2 M MitoSOX dissolved in 0.4% pluronic acid F-127, 0.1% DMSO, 5g/l cremophor, and 1 M N,N,N=,N= tetrakis (2-pyridylmethyl)ethylenediamine (48,52).…”

Section: Methodsmentioning

confidence: 99%

Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

Bhatt

Aon

Tocchetti

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Bhatt NM, Aon MA, Tocchetti CG, Shen X, Dey S, Ramirez-Correa G, O=Rourke B, Gao WD, Cortassa S. Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose. Am J Physiol Heart Circ Physiol 308: H291-H302, 2015. First published December 3, 2014; doi:10.1152/ajpheart.00378.2014.-Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function. contractile work; rate of respiration; redox environment; antioxidant systems; oxidative phosphorylation; mitochondrial ros emission; Zucker diabetic fatty rat A COMMON COMPLICATION OF TYPE 2 diabetes mellitus (T2DM) is cardiomyopathy, characterized by diastolic and systolic dysfunction, which is likely impacted by alterations in metabolic substrate availability. Although the healthy heart is flexible regarding fuel selection, the high levels of glucose and fat in T2DM lead to questions about which factors contribute to dysfunction and which are beneficial as energy source or redox donors (35).Fatty acids (FA) and glucose are the two major fuels driving heart contraction, and in T2DM and obesity existing evidence indicates increased FA oxidation (12, 15). The idea that FAs excess negatively regulates glucose oxidation in diabetes according to the Randle mechanism (33) remains a central postulate explaining some negative consequences of substrate shift in this metabolic disorder. However, it is now increasingly appreciated that hyperglycemia per se can trigger cellular damage, independently from FA utilization (11). The multiple mechanisms throug...

show abstract

“…Myofilament proteins were isolated from mouse hearts as previously described (44). Protein samples were separated by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by Coomassie blue staining as previously described (44).…”

Section: Methodsmentioning

confidence: 99%

Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease

et al. 2012

View full text Add to dashboard Cite

Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actinbound regulatory proteins play a dominant role in the activation of calcium-dependent cardiac muscle contraction. In contrast, the relevance and nature of regulation by myosin regulatory proteins (for example, myosin light chain-2 [MLC2]) in cardiac muscle remain poorly understood. By integrating gene-targeted mouse and computational models, we have identified an indispensable role for ventricular Mlc2 (Mlc2v) phosphorylation in regulating cardiac muscle contraction. Cardiac myosin cycling kinetics, which directly control actin-myosin interactions, were directly affected, but surprisingly, Mlc2v phosphorylation also fed back to cooperatively influence calcium-dependent activation of the thin filament. Loss of these mechanisms produced early defects in the rate of cardiac muscle twitch relaxation and ventricular torsion. Strikingly, these defects preceded the left ventricular dysfunction of heart disease and failure in a mouse model with nonphosphorylatable Mlc2v. Thus, there is a direct and early role for Mlc2 phosphorylation in regulating actin-myosin interactions in striated muscle contraction, and dephosphorylation of Mlc2 or loss of these mechanisms can play a critical role in heart failure.

show abstract

Roles of phosphorylation of myosin binding protein‐C and troponin I in mouse cardiac muscle twitch dynamics

Cited by 76 publications

References 54 publications

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease

Contact Info

Product

Resources

About