Distinct shear-induced Ca2+ signaling in the left and right atrial myocytes: Role of P2 receptor context

Le, Qui Anh; Kim, Joon-Chul; Kim, Kyeong-Hee; Vu, Anh Thi Van; Woo, Sun–Hee

doi:10.1016/j.yjmcc.2020.04.018

Cited by 6 publications

(4 citation statements)

References 55 publications

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“…More specifically, shear stresses and their gradients have been reported to upregulate

v with

integrin subunits 117–119 and their association with FAs, force–modulated through lipid raft diffusion, 69 and with the adaptor protein Shc. 118 Shear flow is also known to drive upregulation in GJs, as well as the activation of TRP channels, to allow modulation of cations, particularly Ca 2+ , 76,77 which, in turn, results in the triggering of important downstream signaling pathways. These, depending on cell type, include, although are not limited to, the Rho–ROCK pathway in osteoblasts and osteocytes, 78,79 the ERK1/2 MAPK pathway in stem cells 80,81 and ECs, 120,121 or the Wnt/

-catenin pathway in ECs and fibroblasts, 82,83 all of which play a role in modulating multiple cellular activities.…”

Section: Static or Quasi-static Constant-force Mechanostimulationmentioning

confidence: 99%

Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

Ambattu

Yeo

2023

Biophysics Reviews

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All cells possess an innate ability to respond to a range of mechanical stimuli through their complex internal machinery. This comprises various mechanosensory elements that detect these mechanical cues and diverse cytoskeletal structures that transmit the force to different parts of the cell, where they are transcribed into complex transcriptomic and signaling events that determine their response and fate. In contrast to static (or steady) mechanostimuli primarily involving constant-force loading such as compression, tension, and shear (or forces applied at very low oscillatory frequencies ( ≤ 1 Hz) that essentially render their effects quasi-static), dynamic mechanostimuli comprising more complex vibrational forms (e.g., time-dependent, i.e., periodic, forcing) at higher frequencies are less well understood in comparison. We review the mechanotransductive processes associated with such acoustic forcing, typically at ultrasonic frequencies ( > 20 kHz), and discuss the various applications that arise from the cellular responses that are generated, particularly for regenerative therapeutics, such as exosome biogenesis, stem cell differentiation, and endothelial barrier modulation. Finally, we offer perspectives on the possible existence of a universal mechanism that is common across all forms of acoustically driven mechanostimuli that underscores the central role of the cell membrane as the key effector, and calcium as the dominant second messenger, in the mechanotransduction process.

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“…More specifically, shear stresses and their gradients have been reported to upregulate

v with

-catenin pathway in ECs and fibroblasts, 82,83 all of which play a role in modulating multiple cellular activities.…”

Section: Static or Quasi-static Constant-force Mechanostimulationmentioning

confidence: 99%

Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

Ambattu

Yeo

2023

Biophysics Reviews

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“…In contrast to our observations on mechanically non-loaded CM, we showed that short-term AF resulted in the depressed auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM. The inter-atrial differences in the stress response between LA and RA CM, which were recently demonstrated ( 84 ) may contribute to observed results and warrant further studies.…”

Section: Discussionmentioning

confidence: 59%

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

Butova

Myachina

Simonova

et al. 2023

Front. Cardiovasc. Med.

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IntroductionThe left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms.MethodsWe investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl2 AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca2+]i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay.ResultsAF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM.DiscussionThus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.

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“…These differences may in part be related to the extent and relation of mechanical, neurohumoral and possibly paracrine stress sensed by the RA vs. the LA. In addition, an intrinsic diversity in the stress response between RA and LA cardiomyocytes was recently suggested, which may contribute to our observed differences between LA and RA and warrants further study 29 …”

Section: Discussionmentioning

confidence: 71%

“…In addition, an intrinsic diversity in the stress response between RA and LA cardiomyocytes was recently suggested, which may contribute to our observed differences between LA and RA and warrants further study. 29 The sarcolemmal NCX exports Ca out of the cytosol in exchange for Na (forward mode) generating a potentially arrhythmogenic depolarizing inward current. NCX inhibitors have shown to reduce arrhythmias and also have the potential to increase cardiomyocyte inotropy by augmenting cytosolic Ca.…”

Section: Discussionmentioning

confidence: 99%

Cellular contribution to left and right atrial dysfunction in chronic arterial hypertension in pigs

et al. 2020

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Aims Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease (HHD), but the role of cardiomyocyte dysfunction in atrial remodelling in HHD is not well understood. We investigated and compared cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in pigs with HHD. Methods and results In vivo electrophysiological and magnetic resonance imaging studies were performed in control and pigs treated with 11‐deoxycorticosterone acetate (DOCA)/high‐salt/glucose diet (12 weeks) to induce HHD. HHD leads to significant atrial remodelling and loss of contractile function in LA and a similar trend in RA (magnetic resonance imaging). Atrial remodelling was associated with a higher inducibility of atrial fibrillation but unrelated to changes in atrial refractory period or fibrosis (histology). Reduced atrial function in DOCA pigs was related to reduced contraction amplitude of isolated LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca release (Fura 2‐AM, field stimulation). However, Ca regulation differed in LA and RA cardiomyocytes: LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca], whereas in RA, SR [Ca] was unchanged and SR Ca2+‐ATPase activity was increased. Sodium–calcium exchanger (NCX) activity was not significantly altered. We used ORM‐10103 (3 μM), a specific NCX inhibitor to improve Ca availability in LA and RA cardiomyocytes from DOCA pigs. Partial inhibition of NCX increased Ca2+ transient amplitude and SR Ca in LA, but not RA cells. Conclusions In this large animal model of HHD, atrial remodelling in sinus rhythm in vivo was related to differential LA and RA cardiomyocyte dysfunction and Ca signalling. Selective acute inhibition of NCX improved Ca release in diseased LA cardiomyocytes, suggesting a potential therapeutic approach to improve atrial inotropy in HHD.

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Distinct shear-induced Ca2+ signaling in the left and right atrial myocytes: Role of P2 receptor context

Cited by 6 publications

References 55 publications

Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

Cellular contribution to left and right atrial dysfunction in chronic arterial hypertension in pigs

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