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The Journal of Physiological Sciences

, Volume 68, Issue 6, pp 759–767 | Cite as

Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats

  • Kimiko Masuda
  • Hiroki Takanari
  • Masaki Morishima
  • FangFang Ma
  • Yan Wang
  • Naohiko Takahashi
  • Katsushige OnoEmail author
Original Paper

Abstract

Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (IKs), whereas IKs was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-IKs possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.

Keywords

Testosterone Electrocardiogram QT interval Potassium channel Kv7.1 

Abbreviations

DHT

Dihydrotestosterone

TdP

Torsades de pointes

QTc

Corrected QT intervals

JTc

Correlated JT interval

Kv

Voltage-gated potassium channel

Kir

Inwardly rectifying potassium channel

KCNQ1

Potassium voltage-gated channel subfamily Q member 1

IK1

Anomalous inwardly rectifying potassium current

Ito

Transient outward potassium currents

IKr

Rapidly activating delayed rectifier potassium currents

IKs

Slowly activating delayed rectifier potassium current

ISO

Isoproterenol

CREB

cAMP response element binding protein

Sp1

Specificity protein 1

Notes

Sources of funding

This work was supported in part by JSPS KAKENHI number 25460292 (K.O.) from the Japan Society for the Promotion of Science, Tokyo.

Compliance with ethical standards

Conflict of interest

All authors have declared that no conflict of interest exists.

Supplementary material

12576_2017_590_MOESM1_ESM.docx (2.1 mb)
Supplementary material 1 (DOCX 2133 kb)

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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Cardiology and Clinical ExaminationOita University School of MedicineYufuJapan
  2. 2.Department of PathophysiologyOita University School of MedicineYufuJapan

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