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. 研究了兔窦房结起搏器细胞的区域差异、形态和功能异质性，并建立了相应的数学模型。动作电位持续时间在窦房结中心最大，向终嵴下降。对膜电流和通道特异性阻滞剂效应的分析表明，这可能是由于快速延迟整流器的K+电流密度较小和中心的4-氨基吡啶敏感持续电流。在终末嵴表达connexin43的心房肌细胞和表达connexin45 /connexin40的窦房结细胞之间有明显的界限，但在心内膜侧，在connexin43和connexin45表达融合的地方检测到一个过渡区。ryanodine阻断肌浆网释放的Ca - γ - D12+ γ - D1，使起搏器的主要部位从窦房结中心向中隔转移。在外围区，ryanodine抑制舒张舒张，c去极化较多，常引起不规则的兴奋，而在中心区，ryanodine未引起动作电位的实质性变化。这些结果表明，肌浆网Ca - γ - D12+ γ - D1的释放在外周可能比在中枢发挥更重要的作用。电刺激节后迷走神经引起短暂的起搏器向靠近上腔静脉或下腔静脉的外周移动。这可能反映了窦房结细胞对乙酰胆碱反应性的区域差异。基于膜电流数据建立了窦房结外围和中心动作电位的数学模型。模拟的动作电位与实验记录的一致，模型对各种离子通道阻断的反应行为也与实验观察到的定性相同。在考虑区域异质性的一维模型中，自发激励从中心开始向周边传播。这些模型为研究窦房结起搏器细胞的异质性和区域差异的生理意义提供了有用的工具。少

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。

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。

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。

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。