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Studies on the developmental changes and species difference of cardiac function : analysis of the electrophysiological characteristics and specific responses to alpha-adrenergic stimulation in mice

心脏功能的发育变化和物种差异的研究：小鼠电生理特征和对α-肾上腺素能刺激的特异性反应分析

基本信息

批准号：
09670107
负责人：
KOKI Shigenobu
金额：
$ 1.98万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Specificity of mice myocardium and its functional changes during development were examined from various points of veiw (electrophysiology, contractile mechanisms, drug sensitivity, etc.). Main results obtained are as follows.1)Action potentials with relatively long duration at neonatal stages were changed into those with extremetly short duration without plateau phase in the adult. This characteristic action potential configuration was considered to be due to small calcium current and large transient outward current, which was essentially the same as that observed in rat myocardium. During development, calcium current seemed to decrease with age.2)Contraction of adult myocardium was suggested to be highly dependent on SR function whereas the dependency was low in neonatal myocardium. This change was qualitatively similar to that observed in rat myocardium, but the degree of developmental change was small compared to rat.3)Developmental conversion of inotropism from positive to negative was observed in the responses to endothelin I and angiotensin II, which was similar to that observed with alpha-adrenergic stimulation. Receptor subtypes did not change during development (ETA and AT1, respectively)4)Acetylcholine produced positive inotropic response in mouse atria, which was totally different from other animal species. On the basis of various experimental results, it was suggested that acetylcholine may release prostaglandin(s) from endocardial endothelial cells, which in turn producced positive inotropism.

从不同角度（电生理学、收缩机制、药物敏感性等）检查小鼠心肌的特异性及其在发育过程中的功能变化。主要结果如下： 1)将新生儿期持续时间较长的动作电位改为成人期持续时间极短、无平台期的动作电位。这种特征性动作电位构型被认为是由于钙电流小和瞬时外向电流大，这与在大鼠心肌中观察到的基本相同。在发育过程中，钙电流似乎随着年龄的增长而降低。2）成人心肌的收缩高度依赖于SR功能，而新生儿心肌的依赖性较低。这种变化在性质上与大鼠心肌中观察到的变化相似，但发育变化的程度与大鼠相比较小。3)在内皮素I和血管紧张素II的反应中观察到正性肌力向阴性的发育转变，这与α-肾上腺素能刺激时观察到的情况相似。受体亚型在发育过程中没有变化（分别为ETA和AT1）4）乙酰胆碱在小鼠心房中产生正性肌力反应，这与其他动物物种完全不同。根据各种实验结果，有人提出乙酰胆碱可以从心内膜内皮细胞释放前列腺素，进而产生正性肌力作用。