Nordin C
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Physiol. 1997 Apr;272(4 Pt 2):H1838-56. doi: 10.1152/ajpheart.1997.272.4.H1838.
Computer simulations based on a model of transmembrane currents and intracellular Ca2+ flux of an isolated guinea pig myocyte [Nordin, C. Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H2117-H2136, 1993] have previously shown that very small heterogeneous ventricular myocardial syncytia can be constructed in which trains of sustained, nondriven action potentials are initiated and terminated with critically timed premature stimulations by a nonreentrant mechanism. A more detailed examination of the characteristics of such syncytia and the nature of the responses is explored. When cells with the normal configuration of equations were connected by high-resistance gap junctions to other cells in which their configuration was modified to reproduce a myocyte with mild Ca2+ overload and two regenerative levels of diastolic potential, critically timed stimulations shifted the electrical response of the syncytium between a stable phase, in which all myocytes were quiescent until stimulated and generated full action potentials from resting potentials between -90 and -65 mV, and an oscillatory phase, in which all cells generated sustained trains of nondriven action potentials from takeoff potentials between -70 and -30 mV. The following predominant responses were observed in such syncytia: 1) a range of 40-60 ms starting at the refractory period with an inverse relationship between prematurity of the stimulation and time to the first upstroke of nondriven activity, followed by a much shorter period with a direct relationship; 2) a delay shorter than a full compensatory pause following single premature stimulations that do not terminate spontaneous action potentials; and 3) entrainment of nondriven action potentials with short bursts of stimulations at rates just above the intrinsic rate of spontaneous activity and termination at faster rates. The propensity to develop nondriven action potentials was enhanced by Ca2+ loading. Other simulations demonstrated that activity can propagate in syncytia of >100 myocytes from small foci to generate full action potentials in larger regions of normal cells. Analysis of the model shows that these patterns arise primarily from crucial, dynamic relationships among membrane potential, intracellular Ca2+ cycling, and gap junction currents. The results suggest that highly localized interactions between normal and depolarized myocytes in uncoupled heterogeneous syncytia may reproduce many of the characteristic responses of ventricular tachycardia.
基于分离的豚鼠心肌细胞跨膜电流和细胞内Ca2+通量模型的计算机模拟研究[诺丁，C. 《美国生理学杂志》265卷（心脏循环生理学34）：H2117 - H2136，1993年]此前已表明，可构建非常小的异质性心室肌细胞合胞体，在其中通过非折返机制，以严格定时的过早刺激引发并终止持续的、非驱动性动作电位序列。本文对这类合胞体的特征及反应性质进行了更详细的研究。当具有正常方程配置的细胞通过高电阻缝隙连接与其他细胞相连时，后一类细胞的配置经修改以模拟轻度Ca2+过载及两个舒张电位再生水平的心肌细胞，严格定时的刺激可使合胞体的电反应在稳定期和振荡期之间转换。在稳定期，所有心肌细胞均处于静息状态，直至受到刺激并从 - 90至 - 65 mV的静息电位产生完整动作电位；在振荡期，所有细胞从 - 70至 - 30 mV的起始电位产生持续的非驱动性动作电位序列。在这类合胞体中观察到以下主要反应：1）从不应期开始，持续40 - 60 ms，刺激的过早程度与非驱动性活动首次上升的时间呈反比关系，随后是一段短得多的呈正比关系的时期；2）单个未终止自发动作电位的过早刺激后，延迟短于完全代偿性间歇；3）以略高于自发活动固有频率的速率进行短串刺激可使非驱动性动作电位被捕捉，并以更快速率终止。Ca2+负载增强了产生非驱动性动作电位的倾向。其他模拟表明，活动可在由小病灶引发的100多个心肌细胞的合胞体中传播，从而在更大区域的正常细胞中产生完整动作电位。对该模型的分析表明，这些模式主要源于膜电位、细胞内Ca2+循环和缝隙连接电流之间关键的动态关系。结果表明，在未耦合的异质性合胞体中，正常和去极化心肌细胞之间高度局部化的相互作用可能重现室性心动过速的许多特征性反应。
