Stretch Activated Channel Activation can Promote or Suppress Cardiac Alternans

Abstract

Alternans has been linked to the onset of ventricular fibrillation and ventricular tachycardia, leading to life-threatening arrhythmias. Experimentally electromechanical alternans can be either concordant (Long/Short APD corresponds to a Large/Small Ca transient on alternate beats) or discordant (Long/Short APD corresponds to a Small/Large Ca transient). Our previous studies have shown that these phenomena depend on the underlying instability mechanisms (voltage driven or Ca driven) and bi-directional coupling between voltage and Ca cycling. The Large Ca transients also cause larger contractions which can activate mechanically (or stretch) activated currents (SACs). Here, we show how SAC activation can feed back to alter cardiac alternans, using a physiologically detailed rabbit AP and Ca cycling model coupled with SAC (either as Cl current or nonselective cation current). We found that (1) SAC suppresses electromechanically concordant alternans, because SAC shortens longer APD more than the shorter APD and limits the difference between successive APDs, (2) SAC enhances electromechanically discordant alternans, because SAC shortens the Short APD more than Long APD which amplifies the difference of two successive APDs. Qualitatively similar results were found for Cl-selective and non-selective cation current (and also Ca-activated K current). These results suggest that mechano-electric feedback can play an important role in development and stability of cardiac alternans.