Kline R P, Sorota S, Dresdner K P, Steinhelper M E, Lanson N A, Wit A L, Claycomb W C, Field L J
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
J Cardiovasc Electrophysiol. 1993 Dec;4(6):642-60. doi: 10.1111/j.1540-8167.1993.tb01251.x.
We have generated transgenic animals that heritably develop atrial tumors composed of differentiated proliferating cardiomyocytes. Experiments were initiated to characterize the electrical properties of these cells.
We show that the primary atrial tumors are composed of discrete foci that exhibit spontaneous automatic activity. A direct correlation was observed between tumor size and firing rate of these foci. In addition to the primary atrial tumors, we examined the properties of cultured cardiomyocytes isolated from a transplantable transgenic tumor lineage (designated AT-1 cells). Cultured AT-1 cells are also spontaneously automatic. The action potential configuration from these preparations is similar to that observed in nontransgenic atrial cardiomyocytes, albeit somewhat more depolarized and of longer duration. As would be expected for cardiomyocytes of atrial origin, the transgenic cardiomyocyte preparations hyperpolarize during muscarinic stimulation due to increased K+ conductance mediated by a pertussis toxin sensitive G-protein. Assessment of pharmacologic blockage of the "if" pacemaker current suggests that the automaticity of both transgenic cardiomyocyte preparations may be of novel origin. In this context, the cultured AT-1 cells showed spontaneous behavior that was clearly of cellular origin; this activity was manifest as transient bursts of electrical activity followed by periods of electrical quiescence. This bursting pattern is unusual for normal adult cardiomyocytes, but has been observed in several other cell types. In the primary tumors, automatic behavior may arise from a similar cellular origin or alternatively from a microreentrant phenomena.
Primary tumors and AT-1 cells show essential atrial electrophysiology with important novel features.
我们已培育出可遗传地发展出由分化的增殖心肌细胞组成的心房肿瘤的转基因动物。已开展实验以表征这些细胞的电特性。
我们发现原发性心房肿瘤由表现出自发性自律活动的离散病灶组成。观察到肿瘤大小与这些病灶的发放频率之间存在直接相关性。除了原发性心房肿瘤，我们还研究了从可移植的转基因肿瘤谱系（命名为AT - 1细胞）分离出的培养心肌细胞的特性。培养的AT - 1细胞也具有自发性自律性。这些制剂的动作电位形态与在非转基因心房心肌细胞中观察到的相似，尽管去极化程度略高且持续时间更长。正如心房来源的心肌细胞所预期的那样，转基因心肌细胞制剂在毒蕈碱刺激期间由于百日咳毒素敏感的G蛋白介导的钾离子电导增加而发生超极化。对“if”起搏电流的药理学阻断评估表明，两种转基因心肌细胞制剂的自律性可能源于新的机制。在这种情况下，培养的AT - 1细胞表现出明显源于细胞的自发行为；这种活动表现为短暂的电活动爆发，随后是电静息期。这种爆发模式对于正常成年心肌细胞来说是不寻常的，但在其他几种细胞类型中也有观察到。在原发性肿瘤中，自律行为可能源于类似的细胞机制，或者源于微折返现象。
原发性肿瘤和AT - 1细胞表现出具有重要新特征的基本心房电生理学特性。
