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Studies on the developmental and species difference of the cardiac function: return to chick embryonic myocardium and the integration of the study

心功能发育及物种差异研究：回归鸡胚心肌及研究整合

基本信息

批准号：
17590229
负责人：
SHIGENOBU Kouki
金额：
$ 2.24万
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：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1. Mouse myocardium(1) From the experimental results, it was concluded that Na+, Ca2+-exchanger produces the efflux of Ca2+ and influx of Na+ at the later phase of action potential on the basis of its equilibrium potential, which in turn elicits net inward current, thus contributing the formation of late plateau.(2) Negative inotropic response of mouse myocardium to the alpha-adrenergic stimulation was mainly due to the augmentation of Na+, Ca2+-exchange. The increase in the sensitivity of contractile protein to Ca2+ is caused by the intracellular alkalization. Specially designed contracture experiments suggested that Ca2+ handling by SR was not modified by alpha-stimulation.(3) Positive and negative inotropic response to endothelin is caused by the increase in Ca2+ sensitivity of the contractile protein due to the increase in intracellular pH, and increase in the Ca2+ extrusion through the Na+, Ca2+-exchanger, respectively.2. Chick embryonic myocardium(1) A selective inhibitor of T-type Ca2+ channel, R(-)-efonidipine showed the negative inotropic effects on the chick embryonic ventricle, suggesting that Ca2+ influx through the T-type Ca2+ channels contributes the contraction of the myocardium at early stages of development.(2) Calibdotoxin produced the negative inotropic effects on the young embryonic hearts but iberiotoxin did not. Thus, the intermediate conductance K+ channels are present in the early embryonic myocardium, which is characteristic to vascular smooth muscle.

1.（1）实验结果表明，Na ~+，Ca ~（2+）-交换体在动作电位后期，以其平衡电位为基础，产生Ca ~（2+）外排和Na ~+内流，从而产生净内向电流，促进了晚期平台的形成。(2)小鼠心肌对α-肾上腺素能刺激的负性变力反应主要是由于Na ~+、Ca ~（2+）交换增加所致。收缩蛋白对Ca ~（2+）敏感性的增加是细胞内碱性化所致。特别设计的挛缩实验表明，钙离子处理SR不修改α刺激。(3)对内皮素的正性和负性变力性反应分别是由于细胞内pH升高导致收缩蛋白对Ca 2+的敏感性增加，以及通过Na+、Ca 2 +-交换器增加Ca 2+的外排.鸡胚心肌（1）T型钙通道选择性抑制剂R（-）-efonidipine对鸡胚心室肌有负性肌力作用，提示在发育早期心肌收缩过程中，通过T型钙通道的钙内流起作用。(2)Calibdotoxin对幼胚心脏有负性肌力作用，而Iberiotoxin无此作用。因此，中电导K+通道存在于早期胚胎心肌中，这是血管平滑肌的特征。