The developed mechano-chemo-transduction feedback model reproduced autoregulation of cardiomyocyte contraction under physiological loads and predicted arrhythmogenic discordant alternans under excessive mechanical overload.
The first autoregulatory excitation-contraction coupling model incorporating mechano-chemo-transduction successfully reproduces cardiomyocyte contractility autoregulation under physiological loads and arrhythmogenic alternans under pathological overload.
Summary The heart has intrinsic abilities to autoregulate contractile force in response to mechanical load. Recent experimental studies show that cardiomyocytes have mechano-chemo-transduction (MCT) mechanisms that form a closed feedback loop in the excitation-Ca2+ signaling-contraction (E-C) coupling. This closed feedback loop enables autoregulation of contraction in response to mechanical load changes. Here, we develop the first autoregulatory E-C coupling model that couples electrophysiology, Ca2+ signaling, force development and contraction, and MCT feedback. The model recapitulates the experimental data showing that the mechanical load on cardiomyocytes during contraction increases the L-type Ca2+ current, action potential duration, sarcoplasmic reticulum (SR) Ca2+ content, and SR Ca2+ release, giving rise to increased cytosolic Ca2+ transient (MCT-Ca2+ gain) and enhanced contraction. The model also makes non-trivial predictions on the autoregulation of contraction with moderate MCT-Ca2+ gain under a range of physiological load changes, but arrhythmogenic discordant alternans with excessive MCT-Ca2+ gain under pathological overload.
Hatano et al. (Thu,) conducted a other in Cardiac excitation-contraction coupling. Mechano-chemo-transduction (MCT) feedback model vs. Load-free condition / Model without MCT feedback was evaluated on Autoregulation of contractility and arrhythmogenic alternans. The developed mechano-chemo-transduction feedback model reproduced autoregulation of cardiomyocyte contraction under physiological loads and predicted arrhythmogenic discordant alternans under excessive mechanical overload.