Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals

The developmental changes in the excitation–contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and m...

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Main Authors: Shogo Hamaguchi, Naoki Agata, Maika Seki, Iyuki Namekata, Hikaru Tanaka
Format: Article
Language:English
Published: MDPI AG 2024-08-01
Series:Journal of Cardiovascular Development and Disease
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Online Access:https://www.mdpi.com/2308-3425/11/9/267
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author Shogo Hamaguchi
Naoki Agata
Maika Seki
Iyuki Namekata
Hikaru Tanaka
author_facet Shogo Hamaguchi
Naoki Agata
Maika Seki
Iyuki Namekata
Hikaru Tanaka
author_sort Shogo Hamaguchi
collection DOAJ
description The developmental changes in the excitation–contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca<sup>2+</sup> handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation–contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca<sup>2+</sup> extrusion by the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na<sup>+</sup>-Ca<sup>2+</sup> exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function.
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spelling doaj-art-45ccfe6cac6545419a2d7d54ad5773412025-08-20T01:55:34ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252024-08-0111926710.3390/jcdd11090267Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental AnimalsShogo Hamaguchi0Naoki Agata1Maika Seki2Iyuki Namekata3Hikaru Tanaka4Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanThe developmental changes in the excitation–contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca<sup>2+</sup> handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation–contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca<sup>2+</sup> extrusion by the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na<sup>+</sup>-Ca<sup>2+</sup> exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function.https://www.mdpi.com/2308-3425/11/9/267myocardiumdevelopmentaction potentialCa<sup>2+</sup> handlinginotropyadrenoceptors
spellingShingle Shogo Hamaguchi
Naoki Agata
Maika Seki
Iyuki Namekata
Hikaru Tanaka
Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
Journal of Cardiovascular Development and Disease
myocardium
development
action potential
Ca<sup>2+</sup> handling
inotropy
adrenoceptors
title Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
title_full Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
title_fullStr Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
title_full_unstemmed Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
title_short Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
title_sort developmental changes in the excitation contraction mechanisms of the ventricular myocardium and their sympathetic regulation in small experimental animals
topic myocardium
development
action potential
Ca<sup>2+</sup> handling
inotropy
adrenoceptors
url https://www.mdpi.com/2308-3425/11/9/267
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