Heqing Zhan1, Jingtao Zhang2, Anquan Jiao3, Qin Wang3. 1. College of Medical Information, Hainan Medical University, Haikou, 571199, China. zhq86zijing@163.com. 2. Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, 100037, China. 3. College of Medical Information, Hainan Medical University, Haikou, 571199, China.
Abstract
BACKGROUND: The 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. RESULTS: Our results indicated that these three currents significantly regulated myocyte mechanical parameters. In isosarcometric contraction, these currents increased segment force by 13.8-36.6% and dropped element length by 12.1-31.5%. In isotonic contraction, there are 2.7-5.9% growth and 0.9-24% reduction. Effects of these currents on the extremum of myocyte mechanical parameters become more significant with the increase of basic cycle length, number of coupled Mfbs and intercellular coupling conductance. CONCLUSIONS: The results demonstrated that stretch-activated current in myocytes and Na+ current and mechano-gated channels' current in Mfbs significantly influenced myocyte mechanical behavior and should be considered in future cardiac mechanical mathematical modeling.
BACKGROUND: The 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. RESULTS: Our results indicated that these three currents significantly regulated myocyte mechanical parameters. In isosarcometric contraction, these currents increased segment force by 13.8-36.6% and dropped element length by 12.1-31.5%. In isotonic contraction, there are 2.7-5.9% growth and 0.9-24% reduction. Effects of these currents on the extremum of myocyte mechanical parameters become more significant with the increase of basic cycle length, number of coupled Mfbs and intercellular coupling conductance. CONCLUSIONS: The results demonstrated that stretch-activated current in myocytes and Na+ current and mechano-gated channels' current in Mfbs significantly influenced myocyte mechanical behavior and should be considered in future cardiac mechanical mathematical modeling.