{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:40:27Z","timestamp":1786977627115,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T00:00:00Z","timestamp":1709942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats: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\u2013postnatal period heart rate changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The APs of true pacemaker cells at different stages had similar configurations and\n                      <jats:italic>dV<\/jats:italic>\n                      \/\n                      <jats:italic>dt<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      values. The cycle length, action potential duration (APD\n                      <jats:sub>90<\/jats:sub>\n                      ), 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\n                      <jats:sup>2+<\/jats:sup>\n                      and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization\u2013activated pacemaker \u0441urrent (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>f<\/jats:italic>\n                      <\/jats:sub>\n                      ) decreased during development, whereas transmembrane and intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      flows increased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The ontogenetic decrease in\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>K1<\/jats:sub>\n                      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 \u201cmembrane\u2010clock\u201d to the \u201ccalcium\u2010clock.\u201d\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dvdy.701","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T08:53:32Z","timestamp":1709974412000},"page":"895-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.1002","volume":"253","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6958-0854","authenticated-orcid":false,"given":"Alexander","family":"Ryvkin","sequence":"first","affiliation":[{"name":"Ben Gurion University of Negev  Beer Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2981-5898","authenticated-orcid":false,"given":"Arseniy","family":"Furman","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology, Institute of Physiology, Komi Science Center Ural Branch of the Russian Academy of Sciences  Syktyvkar Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-9162","authenticated-orcid":false,"given":"Elena","family":"Lebedeva","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology, Institute of Physiology, Komi Science Center Ural Branch of the Russian Academy of Sciences  Syktyvkar Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0860-1252","authenticated-orcid":false,"given":"Mikhail","family":"Gonotkov","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology, Institute of Physiology, Komi Science Center Ural Branch of the Russian Academy of Sciences  Syktyvkar Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576\u2010012\u20100248\u20101"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.03.022"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206078"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.11.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.165"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008\u20106363(00)00135\u20108"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.178145"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021728"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1139\/y01\u2010085"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00253.2016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12447"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.56.030194.002413"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00143.2010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.12.013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2019.08.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"MarkovN LebedevaE GonotkovM AlexanderR.In Silico study of the ontogenetic changes in action potential properties of mouse cardiac pacemaker cells.In 2021 IEEE Ural\u2010Siberian Conference on Computational Technologies in Cognitive Science Genomics and Biomedicine (CSGB). 2021; 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