Alexander Ryvkin, Arseniy Furman, Elena Lebedeva, Mikhail Gonotkov
{"title":"小鼠中房结真起搏细胞在体外和体内发育过程中的动作电位形态变化分析","authors":"Alexander Ryvkin, Arseniy Furman, Elena Lebedeva, Mikhail Gonotkov","doi":"10.1002/dvdy.701","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre–postnatal period heart rate changes.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The APs of true pacemaker cells at different stages had similar configurations and <i>dV</i>/<i>dt</i><sub>max</sub> values. The cycle length, action potential duration (APD<sub>90</sub>), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni<sup>2+</sup> and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization–activated pacemaker сurrent (<i>I</i><sub><i>f</i></sub>) decreased during development, whereas transmembrane and intracellular Ca<sup>2+</sup> flows increased.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The ontogenetic decrease in <i>I</i><sub>K1</sub> density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the “membrane-clock” to the “calcium-clock.”</p>\n </section>\n </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"895-905"},"PeriodicalIF":2.0000,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Analysis of changes in the action potential morphology of the mouse sinoatrial node true pacemaker cells during ontogenetic development in vitro and in silico\",\"authors\":\"Alexander Ryvkin, Arseniy Furman, Elena Lebedeva, Mikhail Gonotkov\",\"doi\":\"10.1002/dvdy.701\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre–postnatal period heart rate changes.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The APs of true pacemaker cells at different stages had similar configurations and <i>dV</i>/<i>dt</i><sub>max</sub> values. The cycle length, action potential duration (APD<sub>90</sub>), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni<sup>2+</sup> and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization–activated pacemaker сurrent (<i>I</i><sub><i>f</i></sub>) decreased during development, whereas transmembrane and intracellular Ca<sup>2+</sup> flows increased.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The ontogenetic decrease in <i>I</i><sub>K1</sub> density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the “membrane-clock” to the “calcium-clock.”</p>\\n </section>\\n </div>\",\"PeriodicalId\":11247,\"journal\":{\"name\":\"Developmental Dynamics\",\"volume\":\"253 10\",\"pages\":\"895-905\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-03-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Developmental Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/dvdy.701\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Dynamics","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dvdy.701","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
Analysis of changes in the action potential morphology of the mouse sinoatrial node true pacemaker cells during ontogenetic development in vitro and in silico
Background
Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre–postnatal period heart rate changes.
Results
The APs of true pacemaker cells at different stages had similar configurations and dV/dtmax values. The cycle length, action potential duration (APD90), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni2+ and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization–activated pacemaker сurrent (If) decreased during development, whereas transmembrane and intracellular Ca2+ flows increased.
Conclusions
The ontogenetic decrease in IK1 density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the “membrane-clock” to the “calcium-clock.”
期刊介绍:
Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.