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- Title
The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.
- Authors
Shanyu Cui; Hyewon Park; Hyelim Park; Dasom Mun; Seung-Hyun Lee; Hyoeun Kim; Nuri Yun; Hail Kim; Kim, Michael; Hui-Nam Pak; Moon-Hyoung Lee; Boyoung Joung
- 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 freshlyisolated 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.
- Subjects
SEROTONIN; FETAL development; CELL membranes; ELECTROCARDIOGRAPHY; PREGNANCY; THERAPEUTICS
- Publication
Yonsei Medical Journal, 2018, Vol 59, Issue 2, p279
- ISSN
0513-5796
- Publication type
Article
- DOI
10.3349/ymj.2018.59.2.279