Stretch-Activated Current Can Promote or Suppress Cardiac Alternans Depending on Voltage-Calcium Interaction

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 (I_SAC) on alternans using a physiologically detailed model of the ventricular myocyte. We found that increasing I_SAC 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 I_SAC promotes Ca alternans. In addition, if action potential duration-Ca transients show quasiperiodicity, we observe a biphasic effect of I_SAC, i.e., suppressing quasiperiodic oscillation at small stretch but promoting electromechanically discordant alternans at larger stretch. Our results demonstrate how I_SAC interacts with coupled voltage-Ca dynamical systems with respect to alternans.