Uniaxial strain of cultured mouse and rat cardiomyocyte strands slows conduction more when its axis is parallel to impulse propagation than when it is perpendicular

Buccarello, Andrea; Azzarito, Michela; Michoud, Frédéric; Lacour, Stéphanie; Kučera, Jan

doi:10.1111/apha.13026

Cited by 9 publications

(15 citation statements)

References 56 publications

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“…Cultures of ventricular myocytes from neonatal (0–1 day postpartum) or fetal (19.5 days postcoitum) wild‐type C57BL/6J mice (Charles River) were prepared according to previously published protocols (Beauchamp et al., 2004; Buccarello et al., 2018; Prudat & Kucera, 2014). The animals had ad libitum access to food and water.…”

Section: Methodsmentioning

confidence: 99%

“…The stretching system, described in detail previously (Buccarello et al., 2018), consisted of four linear motorized stages (MTS25‐Z8; Thorlabs) arranged in a symmetric manner along four perpendicular directions. The stages carried supports for printed circuit boards.…”

Section: Methodsmentioning

confidence: 99%

“…The markers integrated in the sMEAs were imaged by a camera (B910 HD Webcam; Logitech) positioned underneath. A custom MATLAB (MathWorks) analysis program identified the markers in real time, which enabled us to monitor the applied strain by computing the average deformation gradient tensor in the centre of the sMEA and to adjust the strain to the desired target strain using a closed control loop (Buccarello et al., 2018). In particular, the system made it possible to apply strictly uniaxial strains in the x and y directions by precisely compensating the tendency to constriction of an elastic material along axes orthogonal to the main direction of stretch.…”

Section: Methodsmentioning

confidence: 99%

“…Polydimethylsiloxane (PDMS)‐based sMEAs were micro‐fabricated using a previously published process (Buccarello et al., 2018). In brief, 100‐mm silicon wafers were spin‐coated with poly(4‐styrenesulfonic acid) (PSS; 18 wt.…”

Section: Methodsmentioning

confidence: 99%

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Active force generation contributes to the complexity of spontaneous activity and to the response to stretch of murine cardiomyocyte cultures

Nayir

Lacour²,

Kučera

2022

The Journal of Physiology

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Cardiomyocyte cultures exhibit spontaneous electrical and contractile activity, as in a natural cardiac pacemaker. In such preparations, beat rate variability exhibits features similar to those of heart rate variability in vivo. Mechanical deformations and forces feed back on the electrical properties of cardiomyocytes, but it is not fully elucidated how this mechano‐electrical interplay affects beating variability in such preparations. Using stretchable microelectrode arrays, we assessed the effects of the myosin inhibitor blebbistatin and the non‐selective stretch‐activated channel blocker streptomycin on beating variability and on the response of neonatal or fetal murine ventricular cell cultures against deformation. Spontaneous electrical activity was recorded without stretch and upon predefined deformation protocols (5% uniaxial and 2% equibiaxial strain, applied repeatedly for 1 min every 3 min). Without stretch, spontaneous activity originated from the edge of the preparations, and its site of origin switched frequently in a complex manner across the cultures. Blebbistatin did not change mean beat rate, but it decreased the spatial complexity of spontaneous activity. In contrast, streptomycin did not exert any manifest effects. During the deformation protocols, beat rate increased transiently upon stretch but, paradoxically, also upon release. Blebbistatin attenuated the response to stretch, whereas this response was not affected by streptomycin. Therefore, our data support the notion that in a spontaneously firing network of cardiomyocytes, active force generation, rather than stretch‐activated channels, is involved mechanistically in the complexity of the spatiotemporal patterns of spontaneous activity and in the stretch‐induced acceleration of beating. Key points Monolayer cultures of cardiac cells exhibit spontaneous electrical and contractile activity, as in a natural cardiac pacemaker. Beating variability in these preparations recapitulates the power‐law behaviour of heart rate variability in vivo. However, the effects of mechano‐electrical feedback on beating variability are not yet fully understood. Using stretchable microelectrode arrays, we examined the effects of the contraction uncoupler blebbistatin and the non‐specific stretch‐activated channel blocker streptomycin on beating variability and on stretch‐induced changes of beat rate. Without stretch, blebbistatin decreased the spatial complexity of beating variability, whereas streptomycin had no effects. Both stretch and release increased beat rate transiently; blebbistatin attenuated the increase of beat rate upon stretch, whereas streptomycin had no effects. Active force generation contributes to the complexity of spatiotemporal patterns of beating variability and to the increase of beat rate upon mechanical deformation. Our study contributes to the understanding of how mechano‐electrical feedback influences heart rate variability.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Active force generation contributes to the complexity of spontaneous activity and to the response to stretch of murine cardiomyocyte cultures

Nayir

Lacour²,

Kučera

2022

The Journal of Physiology

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“…A model was suggested for explaining these data by setting the membrane capacitance and myocardial conductivity as functions of myocardium strain along muscle fibers 19 . Experiments with cardiac muscle cells immobilized on a stretchable membrane showed a delay between changes in strain and CV probably caused by the delayed caveolae fusion to the cell membrane 20 . The existence of the delay challenges the assumption that the CV slowdown can be arrhythmogenic as one would expect it to reduce spatial variability of CV.…”

Section: Introductionmentioning

confidence: 99%

Effect of strain‐dependent conduction slowing on the re‐entry formation and maintenance in cardiac muscle: 2D computer simulation

Syomin

Galushka

Tsaturyan

2023

Numer Methods Biomed Eng

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The effect of mechano‐electrical feedback on re‐entry formation and maintenance was studied using a model of myocardial electromechanics that accounts for two components of myocardial conductivity and delayed strain‐dependent changes in membrane capacitance that causes a conduction slowing. Two scenarios were simulated in 2D numerical experiments: (i) propagation of an excitation–contraction wave beyond the edge of a nonconductive nonexcitable obstacle; (ii) circulation of a re‐entry wave around a nonconductive nonexcitable obstacle. The simulations demonstrated that the delayed strain‐dependent deceleration of the conduction waves promotes the detachment of the excitation‐contraction waves from the sharp edge of an elongated obstacle and modulates the re‐entry waves rotating around a compact obstacle. The data show that the mechano‐electrical feedback, together with an increase in the stimulation frequency and an increase in the excitation threshold, is an arrhythmogenic factor that must be taken into account when analyzing the possibility of the re‐entry formation.

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Induced pluripotent stem cell-derived cardiomyocytes

Regev

Baskin

Dolgopyat

et al. 2021

Recent Advances in iPSC-Derived Cell Types

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Uniaxial strain of cultured mouse and rat cardiomyocyte strands slows conduction more when its axis is parallel to impulse propagation than when it is perpendicular

Abstract: Changes in cardiac conduction velocity caused by acute stretch do not only depend on the magnitude of strain but also on its orientation relative to impulse propagation. This dependence is due to different effects on tissue resistance.

Cited by 9 publications

References 56 publications

Active force generation contributes to the complexity of spontaneous activity and to the response to stretch of murine cardiomyocyte cultures

Active force generation contributes to the complexity of spontaneous activity and to the response to stretch of murine cardiomyocyte cultures

Effect of strain‐dependent conduction slowing on the re‐entry formation and maintenance in cardiac muscle: 2D computer simulation

Induced pluripotent stem cell-derived cardiomyocytes

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