Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats
- 408 Downloads
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.
KeywordsTestosterone Electrocardiogram QT interval Potassium channel Kv7.1
Torsades de pointes
Corrected QT intervals
Correlated JT interval
Voltage-gated potassium channel
Inwardly rectifying potassium channel
Potassium voltage-gated channel subfamily Q member 1
Anomalous inwardly rectifying potassium current
Transient outward potassium currents
Rapidly activating delayed rectifier potassium currents
Slowly activating delayed rectifier potassium current
cAMP response element binding protein
Specificity protein 1
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.