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 (I), whereas I 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-I possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.

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−8.5 ± 0.7, −6.3 ± 1.1 and −3.5 ± 0.4 mV, respectively. c The slope conductance was reduced to 0.44 ± 0.04 by 10 µM W-7, 0.45 ± 0.004 by 1 µM bepridil with 10 µM W-7, 0.39 ± 0.08 by 20 µM W-7, and 0.25 ± 0.05 by 10 µM KN93 at −100 mV. d The slope conductance was reduced to 0.03 ± 0.005 by 10 µM W-7, 0.02 ± 0.003 by 1 µM bepridil with 10 µM W-7, 0.03 ± 0.001 by 20 µM W-7, and 0.03 ± 0.004 by 10 µM KN93 at +20 mV.