Heterogeneity of sinoatrial node pacemaker cells

窦房结起搏细胞的异质性

• 批准号: 10044266
• 负责人: KODAMA Itsuo
• 金额: $ 2.5万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044266/
• 关键词: sinoatrial node; ion channel; action potential; gap junction; pacemaker activity; electrophysiology; immunohistochemistry; simulation; 筋小胞体; 迷走神経

1. Regional differences and morphological and functional heterogeneity of pacemaker cells were investigated in the rabbit sinoatrial (SA) node, and mathematical models were developed.2. Action potential duration was greatest at the center of the SA node and declined to the crista terminalis. Analysis of membrane current and effects of channel-specific blockers revealed that this may be result of smaller density of the rapid delayed rectifier K+ current and the 4-aminopyridine-sensitive sustained current in the center.3. There was a sharply demarcated boundary between connexin43-expressing atrial myocytes in the crista terminalis and connexin 45/connexin40-expressing SA node cells, but on the endocardial side, a transitional zone was detected where connexin43 and connexin45 expression merged.4. Block of CaィイD12+ィエD1 release from sarcoplasmic reticlum by ryanodine shifted the leading pacemaker site from the SA node center toward the septum. In the periphery, ryanodine suppressed diastoli … More c depolarization often resulting in irregular excitation, whereas in the center, ryanodine caused no substantial changes in action potentials. These results suggest that CaィイD12+ィエD1 release from sarcoplasmic reticlum may play more important roles in the periphery than in the center.5. Electrical stimulation of postganglionic vagal nerves caused a transient pacemaker shift toward the periphery close to the superior or inferior vena cava. This may reflect regional differences in the responsiveness of SA node cells to acetylcholine.6. Mathematical models of action potentials in the periphery and center of the SA node were developed based on membrane current data. Simulated action potentials were consistent with those recorded experimentally and model behaviors in response to block of various ion channels were also qualitatively the same as those observed experimentally. In the one dimensional model, incorporating regional heterogeneity, spontaneous excitation initiated in the center and propagated to the periphery. Those models serve useful tools to study the physiological significance of heterogeneity and regional differences of SA node pacemaker cells. Less

1。在兔子（SA）节点中研究了起搏器细胞的区域差异以及形态和功能异质性，并开发了数学模型。2。在SA节点的中心，动作潜在的持续时间最大，并下降到Crista终端。对膜电流的分析和通道特异性阻滞剂的作用表明，这可能是由于快速延迟整流器K+电流的密度较小，并且中心中对4-氨基吡啶敏感的持续电流。3。在Crista末端表达的表达心房肌细胞和连接蛋白45/connexin40表达SA节点细胞之间，在心内膜侧有一个鲜明的划界边界，但是在心内膜侧检测到过渡区域，在connexin43 and Connexin43 and Connexin45表达表达中。 Ryanodine从肌浆中释放的Caiy D12+IE D1释放的块将领先的起搏器位点从SA节点中心转移到隔膜。在外围，ryanodine抑制了腹膜内……更多的c depolarisis通常会导致不规则兴奋，而在中心，ryanodine并没有在动作电位上造成实质性变化。这些结果表明，从肌质网中释放的CAIY D12+IE D1在外围可能起着比中心更重要的作用。5。刺激后神经神经的电刺激导致瞬时起搏器向外围移动，靠近上腔静脉或下腔静脉。这可能反映了SA节点细胞对乙酰胆碱的反应性的区域差异。6。基于膜电流数据开发了SA节点外围和中心的动作电位的数学模型。模拟动作电位与实验记录的动作电位是一致的，并且响应各种离子通道的模型行为在质量上与实验观察到的行为也相同。在一个维度模型中，结合了区域异质性，在中心启动并传播到外围的赞助商增强性。这些模型提供了有用的工具来研究SA节点起搏器细胞异质性和区域差异的物理意义。较少的

项目成果

Zhang H., Holden A.V., Kodama I., Honjo H., Lei M., Varghase T., Boyett M.R.: "Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node"American Journal of Physiology. (in press). (2000)

张 H.、Holden A.V.、Kodama I.、Honjo H.、Lei M.、Varghase T.、Boyett M.R.：“兔窦房结周围和中心动作电位的数学模型”美国生理学杂志。

Itsuo Kodama: "Regional differences in effects of E-4031 within the sinoatrial node"American Journal of Physiology. 276. H793-H802 (1999)

Ituo Kodama：“E-4031 在窦房结内的影响存在区域差异”美国生理学杂志。

Haruo Honjo: "Heterogeneity of 4-aminopyridine-sensitive current in rabbit sinoatrial node cells"American Journal of Physiology. 276. H1295-H1304 (1999)

Haruo Honjo：“兔窦房结细胞中 4-氨基吡啶敏感电流的异质性”美国生理学杂志。

Boyett M.R., Honjo H., Yamamoto M., Nikmaram M.R., Niwa R., Kodama I.: "Regional differences in effects of 4-aminopyridine within the sinoatrial node"American Journal of Physiology. 275. H1158-H1168 (1998)

Boyett M.R.、Honjo H.、Yamamoto M.、Nikmaram M.R.、Niwa R.、Kodama I.：“窦房结内 4-氨基吡啶作用的区域差异”美国生理学杂志。

Mitsuru Yamamoto: "Low-frequency extracellular potentials recorded from the sinoatrial node"Cardiovascular Research. 39. 360-372 (1998)

Mitsuru Yamamoto：“从窦房结记录的低频细胞外电位”心血管研究。