SPONTANEOUS ACTIVITY IN TRANSGENIC MOUSE HEART - COMPARISON OF PRIMARY ATRIAL TUMOR WITH CULTURED AT-1 ATRIAL MYOCYTES
SPONTANEOUS ACTIVITY IN TRANSGENIC MOUSE HEART - COMPARISON OF PRIMARY ATRIAL TUMOR WITH CULTURED AT-1 ATRIAL MYOCYTES
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DOI：
10.1111/j.1540-8167.1993.tb01251.x
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发表时间：
1993-12-01
影响因子：
2.7
通讯作者：
FIELD, LJ
中科院分区：
文献类型：
--
作者：
KLINE, RP;SOROTA, S;FIELD, LJ
介绍：我们已经产生了转基因动物，遗传发展心房肿瘤组成的分化增殖心肌细胞。实验开始表征，这些cells.Methods和结果的电性能：我们表明，原发性心房肿瘤是由离散的病灶，表现出自发性的自动活动。观察到肿瘤大小和这些病灶的放电率之间存在直接相关性。除了原发性心房肿瘤外，我们还研究了从可移植转基因肿瘤谱系（指定为AT-1细胞）中分离的培养心肌细胞的特性。培养的AT-1细胞也是自发的。从这些制剂的动作电位配置是类似于在非转基因心房心肌细胞中观察到的，虽然有点更多的去极化和更长的持续时间。正如对心房起源的心肌细胞所预期的，转基因心肌细胞制剂在毒蕈碱刺激期间由于pe毒素敏感性G蛋白介导的K+电导增加而过度增殖。对“i（f）”起搏电流的药理学阻断的评估表明，两种转基因心肌细胞制剂的自律性可能是新的起源。在这种情况下，培养的AT-1细胞表现出明显的细胞起源的自发行为;这种活动表现为短暂的电活动爆发，随后是电静止期。这种爆发模式在正常成年心肌细胞中是不寻常的，但在其他几种细胞类型中也观察到了。在原发性肿瘤，自动行为可能会出现从一个类似的细胞起源，或者从microreentrant phenomenon.Conclusion：原发性肿瘤和AT-1细胞显示重要的心房电生理与重要的新功能。
Introduction: 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.Methods and Results: 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 pe toxin sensitive G-protein. Assessment of pharmacologic blockage of the ''i(f)'' 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 dearly 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.Conclusion: Primary tumors and AT-1 cells show essential atrial electrophysiology with important novel features.