Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels’ current in myofibroblasts alter myocyte mechanical behavior: a computational study

摘要

BackgroundThe activation of stretch-activated channels (SACs) in cardiac myocytes, which changes the phases of action potential repolarization, is proven to be highly efficient for the conversion of atrial fibrillation. The expression of Na⁺ current in myofibroblasts (Mfbs) regenerates myocytes’ action potentials, suggesting that Mfbs play an active role in triggering cardiac rhythm disturbances. Moreover, the excitation of mechano-gated channels (MGCs) in Mfbs depolarizes their membrane potential and contributes to the increased risk of post-infarct arrhythmia. Although these electrophysiological mechanisms have been largely known, the roles of these currents in cardiac mechanics are still debated. In this study, we aimed to investigate the mechanical influence of these currents via mathematical modeling. A novel mathematical model was developed by integrating models of human atrial myocyte (including the stretch-activated current, Ca²⁺–force relation, and mechanical behavior of a single segment) and Mfb (including our formulation of Na⁺ current and mechano-gated channels’ current). The effects of the changes in basic cycle length, number of coupled Mfbs and intercellular coupling conductance on myocyte mechanical properties were compared.