摘要：SummaryThe heart pumps blood into circulation against vascular resistance and actively regulates the contractile force to compensate for mechanical load changes. Our experimental data show that cardiomyocytes have a mechano-chemo-transduction (MCT) mechanism that increases intracellularCa2+transient to enhance contractility in response to increased mechanical load. This study advances the cardiac excitation-Ca2+signaling-contraction (E-C) coupling model on conceptual and technical fronts. First, we developed analytical and computational models to perform 3-dimensional mechanical analysis of cardiomyocytes contracting in a viscoelastic medium under mechanical load. Next, we proposed an MCT feedback loop in the E-C coupling dynamic system to shift the feedforward paradigm of cardiac E-C coupling to an autoregulation model. Our combined modeling and experimental studies reveal that MCT enables autoregulation of E-C coupling and contractility in single cardiomyocytes, which underlies the heart’s intrinsic autoregulation in compensatory response to load changes in order to maintain the stroke volume and cardiac output.Graphical abstractDisplay OmittedHighlights•Excitation-contraction (E-C) coupling has mechano-chemo-transduction (MCT) feedback•MCT feedback enables autoregulation of E-C coupling when contracting under load•Models for 3D mechanical analyses of cardiomyocytes contraction•Shifts the paradigm of cardiac E-C coupling from feedforward to autoregulation modelBioinformatics; Biomechanics; Biophysics; Mathematical biosciences.
