Spach M S, Dolber P C, Anderson P A
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Circ Res. 1989 Dec;65(6):1594-611. doi: 10.1161/01.res.65.6.1594.
Recent studies of isolated cardiac myocytes have generated the need for detailed information about regional electrophysiological differences in the atrium. We measured the spatial distribution of action potentials in adult and newborn canine right atria. Multiple regional differences in action potential shape and duration were found. The multiple regional differences produced an overall simple pattern: the longest action potentials occurred in the area of the sinus node, and the action potential duration decreased with increasing distance from the sinus node area. To account for the overall pattern, we tested factors considered important in causing atrial action potential shape differences (e.g., electronic interactions). None of the factors tested accounted for the regional differences. We then found regional differences in the responses to pauses, which suggested that differences in the properties of individual cells accounted for the regional repolarization differences. If so, genetic regulation of the regional differences may produce the overall pattern on a developmental basis. Experiments in newborn atria showed that only in the upper crista was the spatial pattern similar to that of the adult; there was little variability in action potential shape and duration in the other areas. As a further test for associated regional differences in cell properties, we examined for differences in the isoform expression of troponin T (TnT1, TnT2, TnT3, and TnT4), a protein important in excitation-contraction coupling. In adults, the greatest proportion of TnT1 occurred in the area of the sinus node, and its proportion decreased with increasing distance from the sinus node area in association with a relative increase in the proportion of TnT2. In newborn atria the relative amount of TnT1 was greatest in the upper crista (similar to adult), but little difference was found in the distribution of the isoforms in the other regions. The correspondence between the regional differences in repolarization and in the expression of the troponin T isoforms in adult and newborn atria suggests that 1) cellular ionic mechanisms vary regionally to coordinate differences in action potential configuration with differences in cell properties that regulate contractility and 2) genetic expression of the systems that regulate repolarization and mechanical cellular properties are under similar developmental and regional control.
近期对分离的心肌细胞的研究引发了对心房区域电生理差异详细信息的需求。我们测量了成年和新生犬右心房动作电位的空间分布。发现动作电位形状和时程存在多个区域差异。这些多个区域差异呈现出一种总体上简单的模式：最长的动作电位出现在窦房结区域，并且动作电位时程随着与窦房结区域距离的增加而减小。为了解释这种总体模式，我们测试了被认为在导致心房动作电位形状差异方面很重要的因素（例如，电相互作用）。所测试的因素均无法解释区域差异。然后我们发现了对停顿反应的区域差异，这表明单个细胞特性的差异导致了区域复极化差异。如果是这样，区域差异的基因调控可能在发育基础上产生这种总体模式。对新生心房的实验表明，只有在上嵴处空间模式与成年时相似；其他区域的动作电位形状和时程几乎没有变化。作为对相关细胞特性区域差异的进一步测试，我们检查了肌钙蛋白T（TnT1、TnT2、TnT3和TnT4）同工型表达的差异，肌钙蛋白T是一种在兴奋 - 收缩偶联中起重要作用的蛋白质。在成年犬中，TnT1的最大比例出现在窦房结区域，并且其比例随着与窦房结区域距离的增加而降低，同时TnT2的比例相对增加。在新生心房中，TnT1的相对量在上嵴处最大（与成年相似），但在其他区域同工型的分布几乎没有差异。成年和新生心房复极化区域差异与肌钙蛋白T同工型表达之间的对应关系表明：1）细胞离子机制在区域上有所不同，以协调动作电位构型差异与调节收缩性的细胞特性差异；2）调节复极化和机械细胞特性的系统的基因表达受到相似的发育和区域控制。
