Figure 5. Estrogen and testosterone differentially affect sensitivity of I_Kr to drugs.

(A) Experimental (top) and simulated (bottom) dose-dependence curves for inhibition of hERG current by E4031 (control — black line), an I_Kr blocker, and after addition of estrogen (E2 — light gray line) and DHT (dark gray line). The curves for each concentration of E2 and DHT are indicated. (B) Simulated APD (50^th beat at a pacing rate of 1000 ms) with 10 nM E4031 in the presence of both E2 and progesterone (late follicular phase — i). (ii) Simulated effects of testosterone (3 nM) on APD with E4031 application. The computed ECG (low traces) shows that QT interval is substantially longer in case (i) than in case (ii).