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The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

 Shanyu Cui  ;  Hyewon Park  ;  Hyelim Park  ;  Dasom Mun  ;  Seung Hyun Lee  ;  Hyoeun Kim  ;  Nuri Yun  ;  Hail Kim  ;  Michael Kim  ;  Hui Nam Pak  ;  Moon Hyoung Lee  ;  Boyoung Joung 
 YONSEI MEDICAL JOURNAL, Vol.59(2) : 279-286, 2018 
Journal Title
Issue Date
*Action Potentials/drug effects ; Animals ; Cell Membrane/drug effects/metabolism ; Animal Disease Models ; Electrocardiography ; Female ; HSC70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Heart Ventricles/drug effects/*metabolism ; Inbred C57BL Mice ; Knockout Mice ; Cardiac/drug effects/metabolism Myocytes ; Potassium Channels/metabolism ; Pregnancy ; Rabbits ; Sprague-Dawley Rats ; Serotonin Receptors, 5-HT3/metabolism ; Serotonin/*metabolism ; Serotonin 5-HT3 Receptor Agonists/pharmacology
QT interval ; Serotonin receptor type 3 ; membrane trafficking ; pregnancy ; serotonin ; voltage-gated K(+) (Kv) current
PURPOSE: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. MATERIALS AND METHODS: We measured current amplitudes and the expression levels of voltage-gated K(+) (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). RESULTS: During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. CONCLUSION: Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
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