Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models.
Mechanoelectric coupling in the heart is well documented and has been suggested as a cause of arrhythmia. One hypothesized mechanism for the stretch sensitivity of cardiac muscle is the presence of stretch-activated channels (SACs). This study uses modeling to explore the influence of SACs on cardiac resting potential, excitation threshold, and action potential in the context of arrhythmia. We added a putative SAC, modeled as a linear, time-independent conductance with reversal potential of -20 or -50 mV, to guinea pig and frog ventricular membrane models. Increased stretch conductance led to resting potential depolarization, a decreased excitation threshold, altered action potential duration, and, under certain conditions, early afterdepolarizations. We conclude that stretch increases cellular excitability, making the heart prone to ectopic activity. Regional effects of stretch on action potential duration can vary and are influenced by factors such as the SAC reversal potential, ionic conditions, and baseline currents, all of which may lead to an increased dispersion of refractoriness throughout the heart and therefore an increased risk of arrhythmia.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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Riemer
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Sobie
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Tung
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001703:Biophysics / Q000379:methods; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology* / Q000503:physiopathology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008465:Mechanoreceptors / Q000502:physiology; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D018408:Patch-Clamp Techniques; D011898:Ranidae; D013997:Time Factors