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

从电生理、收缩机制、药物敏感性等多个角度考察了小鼠心肌的特异性及其在发育过程中的功能变化。主要研究结果如下：1)成人由新生期持续时间较长的动作电位转变为无平台期的极短持续时间的动作电位。这种特征的动作电位构型被认为是由于小的钙电流和大的瞬时外向电流，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减少。2)成年心肌的收缩高度依赖于SR功能，而新生心肌的这种依赖性较低。这一变化在性质上与大鼠心肌的变化相似，但与大鼠相比，发育变化的程度较小。3)内皮素I和血管紧张素II的反应可观察到变力作用从阳性到阴性的发育性转化，这与α-肾上腺素能刺激的反应相似。受体亚型在发育过程中没有改变(分别为ETA和AT1)4)乙酰胆碱在小鼠心房产生正性变力反应，这与其他动物完全不同。根据各种实验结果，推测乙酰胆碱可从心内膜内皮细胞释放前列腺素(S)，从而产生正性变力作用。

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.