The Influence of the Timing of Cyclic Load Application on Cardiac Cell Contraction.

Lior Debbi,Shelly Tzlil,Stavit Drori

doi:10.3389/fphys.2018.00917

Lior Debbi, Shelly Tzlil + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2018.00917

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Abstract

Cardiac cells are subjected to mechanical load during each heart-beat. Normal heart load is essential for physiological development and cardiac function. At the same time, excessive load can induce pathologies such as cardiac hypertrophy. While the forces working on the heart as an organ are well-understood, information regarding stretch response at the cellular level is limited. Since cardiac stretch-response depends on the amplitude and pattern of the applied load as well as its timing during the beating cycle, the directionality of load application and its phase relative to action potential generation must be controlled precisely. Here, we design a new experimental setup, which enables high-resolution fluorescence imaging of cultured cardiac cells under cyclic uniaxial mechanical load and electrical stimulation. Cyclic stretch was applied in different phases relative to the electrical stimulus and the effect on cardiac cell beating was monitored. The results show a clear phase-dependent response and provide insight into cardiac response to excessive loading conditions.

Highlights

Cardiac cells contract against a mechanical load during each heartbeat
Cardiac cells are subjected to mechanical load during each heartbeat and excessive loading can lead to pathologies
Our data demonstrate that after 10–20 min of cyclic mechanical stretch, applied along the cell contraction axis, cardiac cells contract with a phase shift relative to the electrical stimulus

Summary

Introduction

Cardiac cells contract against a mechanical load during each heartbeat. The heart performs optimally within a defined range of hemodynamic load and fails if acutely or chronically overloaded (Zimmermann, 2013). Several methods were developed to study the response of single cardiac cells to applied load and to elucidate the underlying mechano-chemo-transduction mechanism. These methods include stretching a substrate on top of which cells are attached (reviewed in Quinn and Kohl, 2012), using carbon fibers attached to both ends of a cardiac cell (Le Guennec et al, 1990; Cooper et al, 2000; Prosser et al, 2011) and a “cell-in-a-gel” system whereby isolated cardiomyocytes contract against an elastic three dimensional matrix (Jian et al, 2014). Several recent works combining electrical field stimulation with mechanical stimulation, pointed toward a strong dependence between cardiac cell stretch response and the beating phase when stretch is applied (Nishimura et al, 2006; Morgan and Black, 2014)

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