细胞外低钾对心室肌组织钠通道电导影响的计算机仿真研究

The Effects of Hypokalemia on the Na^+ Channel in Cardiac Tissue——A Computer Simulation Study

为了探讨细胞外低钾时引起长QT综合征单向传导阻滞的易损窗增大的原因,我们以改良的LR91一维非均质心室肌组织数学模型为研究对象,定量化研究了Na+通道电导及门控因子空间梯度的变化。同时,还观察了细胞外正常钾浓度和低钾对动作电位时程及各种离子通道电流的影响。实验分为正常组和LQTS组。分别以500、1 000和2 000 ms的刺激周长(BCL)对一维模型施加基础刺激S1(-70μA/μF、1.5 ms)。每10次S1后施加期前刺激S2,S1S2间期以1 ms的步长递减以测量易损窗。结果发现,细胞外低钾、长QT综合征及心率减慢是通过增大失活因子h*j空间分布梯度使GNa空间梯度增大的。结果还显示,细胞外低钾使IK、IK1电流峰值降低,这使LR91一维模型上心肌细胞AP复极延迟并且复极离散度增大。这可能是导致h*j和GNa空间梯度增大的重要原因之一。这些变化使产生单向传导阻滞的易损窗增大并增加室性心律失常的发生。

In order to explore the reason why hypokalemia could increase the vulnerable window （VW） for uni- directional conduction block in Long QT Syndromes （LQTS）, we observed the effect of hypokalemia on the spatial gradients of Na channel conductance （GNa） and gating factors by using the LRgl 1-dimensional heterogeneous virtual cardiac ventricular tissue model quatitively. The computer simulation experiments were divided into two groups, namely control and LQTS groups. The action potential was elicited after the basic stimulus S1 （-- 70μA/μF, 1.5 ms） was given 10 times with basic cycle length （BCL） 500,1 000 and 2 000 ms. To test the VW in unit of time （VWtimc）, the S1-S2 programmed stimuli were used with shortening S1S2 interval at the decrement of 1 ms. At the same time, the spatial gradients of Na channel conductance （GNa） and gating factors, m, h, j, were investigated. The APD and ionic channel currents were also detected under the conditions of normal and lower concentration of K＋ outside of cell. We found that hypokalemia, LQTS and slow pacing rate enhanced the spatial gradient of GN, by in- creasing the spatial gradient of inactive gating factors h ~ j. The results also showed that hypokalemia deduced the peak values of Ik and IK1, which prolonged the action potential duration and enlarged the repolarization dispersion in this 1-D tissue cable model. Possibly these are the important factors to cause the spatial gradient of h ＊ j and GNa en- largement. These changes increase the incidence of unidirectional conduction block of VW, and are vital reasons to increase the possibility of ventricular arrhythmia generation.