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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalYonsei medical journal
Volume59
Issue number2
DOIs
Publication statusPublished - 2018 Mar

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Serotonin
Pregnancy
Tryptophan Hydroxylase
Voltage-Gated Potassium Channels
Ondansetron
Fetal Development
Knockout Mice
Muscle Cells
Mothers
Membranes
Enzymes
Serum

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Cui, Shanyu ; Park, Hyewon ; Park, Hyelim ; Mun, Dasom ; Lee, Seung Hyun ; Kim, Hyoeun ; Yun, Nuri ; Kim, Hail ; Kim, Michael ; Pak, Hui Nam ; Lee, Moon Hyoung ; Joung, Boyoung. / The role of serotonin in ventricular repolarization in pregnant mice. In: Yonsei medical journal. 2018 ; Vol. 59, No. 2. pp. 279-286.
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title = "The role of serotonin in ventricular repolarization in pregnant mice",
abstract = "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.",
author = "Shanyu Cui and Hyewon Park and Hyelim Park and Dasom Mun and Lee, {Seung Hyun} and Hyoeun Kim and Nuri Yun and Hail Kim and Michael Kim and Pak, {Hui Nam} and Lee, {Moon Hyoung} and Boyoung Joung",
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Cui, S, Park, H, Park, H, Mun, D, Lee, SH, Kim, H, Yun, N, Kim, H, Kim, M, Pak, HN, Lee, MH & Joung, B 2018, 'The role of serotonin in ventricular repolarization in pregnant mice', Yonsei medical journal, vol. 59, no. 2, pp. 279-286. https://doi.org/10.3349/ymj.2018.59.2.279

The role of serotonin in ventricular repolarization in pregnant mice. / Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung.

In: Yonsei medical journal, Vol. 59, No. 2, 03.2018, p. 279-286.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of serotonin in ventricular repolarization in pregnant mice

AU - Cui, Shanyu

AU - Park, Hyewon

AU - Park, Hyelim

AU - Mun, Dasom

AU - Lee, Seung Hyun

AU - Kim, Hyoeun

AU - Yun, Nuri

AU - Kim, Hail

AU - Kim, Michael

AU - Pak, Hui Nam

AU - Lee, Moon Hyoung

AU - Joung, Boyoung

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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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