权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

STUDIES ON THE DEVELOPMENTAL AND SPECIES DIFFERENCE OF CARDIAC FUNCTION: FUNCTIONAL ROLE OF ENDOCARDIAL ENDOTHELIUM AND THE ANALYSIS OF PHYSIOLOGICAL SPECIFICITY OF MOUSE MYOCARDIA

心脏功能发育及物种差异的研究：心内膜内皮的功能作用及小鼠心肌的生理特异性分析

基本信息

批准号：
13670100
负责人：
SHIGENOBU Koki
金额：
$ 2.18万
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：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Research results are summarized as follows:1) Since the specific nature of the mouse heart, including negative inotropic response to alpha-adrenergic stimulation, has been found to be closely related to Na+, Ca2+ exchange mechanism (NCX), the selectivity of a newly synthesized compound, SEA0400, was examined in detail. As a result, it was found that SEA0400 selectivity inhibits NCX without affecting Na+ currents, Ca2+ currents, and inwardly rectifying and delayed rectifier K+ currents.2) Ach produces positive inotropic response in mouse atria through the release of prostaglandins from endocardial endothelium. Since in mouse heart, the specific action potential configuration lacking plateau component minimizes the Ca2+ influx, the negative inotropic component through the activation of IKACh becomes small, and thus the positive inotropic response to endothelium-derived prostaglandins is considered to become marked.3) Mouse atria showed specific responses to various agents, including 4-aminopyridine, necardipine, or ryanodine, which can be explained by the specific action potential configuration and highly SR-dependent contractile mechanisms in mouse heart.4) Guinea pig hear gained the specific nature similar to mouse heat by treating with cromakalim, dimethylamiloride, and ouabain, which produces action potential shortening by activating ATP-dependent potassium channels, intracellular alkalization by inhibiting the Na+, H+ exchange, and the increase in intracellular Na+ concentration through the inhibition of Na-pump, respectively.

1）由于小鼠心脏的特异性，包括对α-肾上腺素能刺激的负性变力性反应，与Na+，Ca ~（2+）交换机制（NCX）密切相关，因此我们对新合成的化合物SEA 0400的选择性进行了详细的研究。结果表明，SEA 0400选择性抑制NCX，而不影响Na+电流、Ca ~（2+）电流、内向整流和延迟整流K ~+电流。2）Ach通过从内皮细胞释放β-肾上腺素产生正性肌力反应。由于在小鼠心脏中，缺乏平台组分的特定动作电位构型使Ca 2+内流最小化，通过IKACh激活的负性变力组分变小，因此认为对内皮源性的利多卡因的正性变力反应变得显著。3）小鼠心房对各种药剂显示出特异性反应，包括4-氨基吡啶、奈卡地平或兰尼定，4）色满卡林、二甲氨氯吡咪、哇巴因处理豚鼠心脏，使其获得了类似小鼠热的特异性性质，通过激活ATP依赖性钾通道使动作电位缩短，通过抑制Na+通道使细胞内碱化，H+交换和通过抑制Na-泵增加细胞内Na+浓度。