Analysis of changes in the action potential morphology of the mouse sinoatrial node true pacemaker cells during ontogenetic development in vitro and in silico.

Autor: Ryvkin A; Ben Gurion University of Negev, Beer Sheva, Israel., Furman A; Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch of the Russian Academy of Sciences, Syktyvkar, Russia., Lebedeva E; Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch of the Russian Academy of Sciences, Syktyvkar, Russia., Gonotkov M; Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch of the Russian Academy of Sciences, Syktyvkar, Russia.
Jazyk: angličtina
Zdroj: Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2024 Oct; Vol. 253 (10), pp. 895-905. Date of Electronic Publication: 2024 Mar 09.
DOI: 10.1002/dvdy.701
Abstrakt: 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/dt max values. The cycle length, action potential duration (APD 90 ), 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 2+ and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization-activated pacemaker сurrent (I f ) decreased during development, whereas transmembrane and intracellular Ca 2+ flows increased.
Conclusions: The ontogenetic decrease in I K1 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."
(© 2024 American Association for Anatomy.)
Databáze: MEDLINE
Externí odkaz: