title: Stretch-Activated Current Can Promote or Suppress Cardiac Alternans Depending on Voltage-Calcium Interaction.
abstract: Cardiac alternans has been linked to the onset of ventricular fibrillation and ventricular tachycardia, leading to life-threatening arrhythmias. Here, we investigated the effects of stretch-activated currents (ISAC) on alternans using a physiologically detailed model of the ventricular myocyte. We found that increasing ISAC suppresses alternans if the voltage-Ca coupling is positive or the alternans is voltage driven. However, for electromechanically discordant alternans, which occurs when the alternans is Ca driven with negative voltage-Ca coupling, increasing ISAC promotes Ca alternans. In addition, if action potential duration-Ca transients show quasiperiodicity, we observe a biphasic effect of ISAC, i.e., suppressing quasiperiodic oscillation at small stretch but promoting electromechanically discordant alternans at larger stretch. Our results demonstrate how ISAC interacts with coupled voltage-Ca dynamical systems with respect to alternans.
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, California.
authors.forename: Samuel
authors.initials: S
authors.lastname: Galice
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, California.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, California. Electronic address: dsato@ucdavis.edu.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D004553:Electric Conductivity; D004562:Electrocardiography; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism
chemical_list: D007473:Ion Channels; D014336:Troponin; D002118:Calcium