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

本文从电生理、收缩机制、药物敏感性等多个角度探讨了小鼠心肌的特异性及其发育过程中的功能变化。主要结果如下：1）新生期动作电位持续时间较长，成年期动作电位持续时间极短，无平台期。这种特征性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。2）成年心肌收缩对SR功能依赖性强，而新生心肌收缩对SR功能的依赖性较低。这种变化在性质上与大鼠心肌中观察到的相似，但发育变化的程度与大鼠相比较小。3）在对内皮素I和血管紧张素II的反应中观察到正性变力性向负性的发育转化，这与α-肾上腺素能刺激观察到的相似。受体亚型在发育过程中没有变化（分别为ETA和AT 1）。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，我们认为乙酰胆碱可使内皮细胞释放前列腺素，从而产生正性肌力作用。

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.