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

1)由于小鼠心脏的特殊性质，包括对α-肾上腺素能刺激的负性肌力反应，已被发现与Na+，钙离子交换机制(NCX)密切相关，因此对新合成的化合物SEA0400的选择性进行了详细的考察。结果发现，SEA0400选择性地抑制Ncx，但不影响Na+电流和钙电流，也不影响内向整流和延迟整流钾电流。2)Ach通过心内膜内皮细胞释放前列腺素而产生正性变力反应。由于在小鼠心脏中，缺乏平台成分的特定动作电位构型最大限度地减少了钙离子的内流，通过激活IKACh而产生的负肌力成分变小，因此对内皮衍生前列腺素的正性肌力反应被认为是显著的。3)小鼠心房对包括4-氨基吡啶、奈卡地平或兰诺定在内的各种药物表现出特异的反应，这可以通过小鼠心脏特定的动作电位构型和高度依赖SR的收缩机制来解释。4)豚鼠心脏通过克罗卡林、二甲基米洛利和哇巴因处理获得了与小鼠热相似的特性，通过激活ATP依赖的钾通道产生动作电位缩短，通过抑制Na~+，~+和Na~+抑制细胞内的碱化H+交换，以及通过抑制Na-泵使细胞内Na+浓度升高。

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.