Creat membership Creat membership
Sign in

Forgot password?

Confirm
  • Forgot password?
    Sign Up
  • Confirm
    Sign In
Creat membership Creat membership
Sign in

Forgot password?

Confirm
  • Forgot password?
    Sign Up
  • Confirm
    Sign In
Collection
For ¥0.57 per day, unlimited downloads CREATE MEMBERSHIP Download

toTop

If you have any feedback, Please follow the official account to submit feedback.

Turn on your phone and scan

home > search >

Synergic Effects of beta-Estradiol and Erythromycin on hERG Currents

Author:
Ando, Fumiaki  Kuruma, Akinori  Kawano, Seiko  


Journal:
JOURNAL OF MEMBRANE BIOLOGY


Issue Date:
2011


Abstract(summary):

The incidence rates of long QT syndrome (LQTS) and drug-induced torsades de pointes (TDP) are higher in women than men. Although gonadal steroids are assumed to play an important role in the gender-based differences in cardiac electrophysiological properties, the underlying mechanisms of the gender-based differences are not fully understood. In particular I(Kr), which comprises the repolarization phase of the action potential, has not been well understood in its modulation by sex hormones. To assess this, we examined the effects of the female sex hormone beta-estradiol on the human ether-a-go-go-related gene (hERG)-encoded potassium current stably expressed in human embryonic kidney-293 (HEK) cells. We demonstrated that hERG currents were inhibited by beta-estradiol maximally to 62% of control with an IC(50) of 1.3 mu M and a Hill coefficient of 0.87, which might account for the sex-related differences in LQTS. We also examined whether estrogen modulated drug-induced blocking effects on hERG currents or not. With simultaneous application of 10 mu M erythromycin, which is known to block hERG currents but not in low doses, the blocking effects of beta-estradiol on hERG currents were enhanced. Namely, hERG currents were inhibited maximally to 45.8% of control with an IC(50) of 59 nM (P < 0.02) by beta-estradiol with 10 mu M erythromycin. We conclude here that a significant block of hERG currents by beta-estradiol may account for the sex-related differences in LQTS and the synergic effects of beta-estradiol and erythromycin indicate a higher risk of drug-induced TDP in women than men.


Page:
31---38


VIEW PDF

The preview is over

If you wish to continue, please create your membership or download this.

Create Membership

Similar Literature

Submit Feedback

This function is a member function, members do not limit the number of downloads