Myocardial Cells As Early As The Rhythm Generated By The Dynamic Mechanism Of Depolarization

As the basis of normal life, the beating of heart has been paid much attention for a long time. A kind of arrhythmia, early after-depolarization (EAD), has been the serious threat to the people's health and the quality of life. But the formation mechanism of EAD has not been clear. On the one hand, the cardiac ion channels, which participate in the cardiac action potential, are numerous and complex. On the other hand, most of the studies about currents are concentrated on the description of biological phenomena, while little studies on the deep formation mechanisms.Following the further combination between life science and nonlinear dynamics, the method of the nonlinear dynamics has gradually used to reveal the mechanism of cardiac rhythm, and has been a hotspot. The novel angle provides a new pathway to learn more information about the cardiac rhythm in the theoretical level. In this paper, the method of the nonlinear dynamics is employed to study EAD being as a boring arrhythmia. On the basis of qualitative and quantitative description of EAD, the dynamics and formation mechanisms of EAD are identified.In this study, the stable EAD rhythms are recorded in an experimental model--cultured cardiac myocytes by cardiac electrophysiology experiments. At the same time, the EAD rhythms are simulated and analyzed in the theoretical level by a mathematical network model, which is composed of heterogeneous units described by Morris-Lecar (ML) model with nearest-neighbor coupling method.The main results were as follows:1. Synchronized EAD rhythms of intracellular calcium concentration ([Ca2+]i) oscillation were discovered in different cells in cultured cardiac myocytes network, using Fura-2/AM staining method. EAD-like oscillation of membrane potential was recorded in a single cell located in the network, using patch clamp. The EAD was the abnormal depolarization generated during the repolarization, being as an immature action potential.2. A network composed of heterogeneous units described by Morris-Lecar (ML) model with nearest-neighbor and electronic coupling method was employed to simulate the cultured cardiac myocytes. To insure the different parameter configuration of the unit oscillation, the parameters of unit oscillators was chosen randomly in a region. The dynamics of unit oscillator are different correspondingly. When the parameters of unit oscillator are chosen near Hopf bifurcation point from period 1 rhythm to depolarized rest, the behaviors are either depolarized rest or period 1 rhythm. Synchronized period 1 rhythms are simulated in the deterministic network whose cells exhibit different rhythms when the coupling strength is increased. Considering the fact that the stochastic factors similar to noise is inevitable in the real cardiac cells, the network containing stochastic component are chosen to further simulate the cardiac cells in the experiment. The synchronous degree of rhythms of the cardiac cells is enhanced by increase of the coupling strength in the stochastic network. Under the influence of noise, the synchronous degree of rhythms is slightly decreased, and the synchronized phenomenon did not change, but the synchronized period 1 rhythm is changed into synchronized EAD rhythm.The Hopf bifurcation point is the critical point from depolarized rest to period 1 rhythm. Under the influence of noise, the behavior of the network is stochastic transition between the depolarized rest and period 1 rhythm. It is the characteristics and dynamics of the EAD rhythm.The above results indicate that EAD rhythm is the synchronized stochastic oscillation of cardiac myocytes or the network near a Hopf bifurcation point. When the behavior or parameters of the oscillator is far from the Hopf bifurcation, the synchronized network of cardiac myocytes is period 1 rhythm or rest. It shows that the heterogeneous network of cardiac myocytes has the capability to produce various synchronous rhythms by itself, including the "regular rhythm" (period 1 rhythm) and "abnormal rhythm" (EAD rhythm). The difference of the various rhythms is the parameters configuration of system, which can lead the system to transit between the different rhythms. The results provide novel understanding for the formation and transition of cardiac myocytes rhythm, and new way to prevent, diagnose and treat the arrhythmia induced by EAD.