Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation

Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SE...

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Main Authors: Shogo Hamaguchi, Ikue Morinou, Yuko Shiseki, Ayako Mikami, Maika Seki, Iyuki Namekata, Hikaru Tanaka
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3926
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author Shogo Hamaguchi
Ikue Morinou
Yuko Shiseki
Ayako Mikami
Maika Seki
Iyuki Namekata
Hikaru Tanaka
author_facet Shogo Hamaguchi
Ikue Morinou
Yuko Shiseki
Ayako Mikami
Maika Seki
Iyuki Namekata
Hikaru Tanaka
author_sort Shogo Hamaguchi
collection DOAJ
description Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SEA0400, a selective Na<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibitor. Phenylephrine increased the L-type Ca<sup>2+</sup> channel current and prolonged the action potential duration, while the voltage-dependent K<sup>+</sup> channel current was not influenced. In the presence of cromakalim, an ATP-sensitive K<sup>+</sup> channel opener, the phenylephrine-induced prolongation of action potential duration, as well as the positive inotropy, were smaller than in the absence of cromakalim. These results suggest that the α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca<sup>2+</sup> influx through the L-type Ca<sup>2+</sup> channel, and the concomitant increase in action potential duration acts as an enhancing factor.
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spelling doaj.art-548858318c4f4d3aa3f41973cbbe50902023-11-16T21:07:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244392610.3390/ijms24043926Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential ProlongationShogo Hamaguchi0Ikue Morinou1Yuko Shiseki2Ayako Mikami3Maika Seki4Iyuki Namekata5Hikaru Tanaka6Department of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanDepartment of Pharmacology, Faculty of Pharmacological Science, Toho University, Chiba 274-8510, JapanMechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SEA0400, a selective Na<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibitor. Phenylephrine increased the L-type Ca<sup>2+</sup> channel current and prolonged the action potential duration, while the voltage-dependent K<sup>+</sup> channel current was not influenced. In the presence of cromakalim, an ATP-sensitive K<sup>+</sup> channel opener, the phenylephrine-induced prolongation of action potential duration, as well as the positive inotropy, were smaller than in the absence of cromakalim. These results suggest that the α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca<sup>2+</sup> influx through the L-type Ca<sup>2+</sup> channel, and the concomitant increase in action potential duration acts as an enhancing factor.https://www.mdpi.com/1422-0067/24/4/3926mouse ventricleα-adrenergic receptorL-type Ca<sup>2+</sup> channelaction potential duration
spellingShingle Shogo Hamaguchi
Ikue Morinou
Yuko Shiseki
Ayako Mikami
Maika Seki
Iyuki Namekata
Hikaru Tanaka
Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
International Journal of Molecular Sciences
mouse ventricle
α-adrenergic receptor
L-type Ca<sup>2+</sup> channel
action potential duration
title Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
title_full Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
title_fullStr Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
title_full_unstemmed Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
title_short Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation
title_sort mechanisms for the α adrenoceptor mediated positive inotropy in mouse ventricular myocardium enhancing effect of action potential prolongation
topic mouse ventricle
α-adrenergic receptor
L-type Ca<sup>2+</sup> channel
action potential duration
url https://www.mdpi.com/1422-0067/24/4/3926
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