Effect of androgen deficiency on mouse ventricular repolarization.
We previously demonstrated that female mouse ventricles have longer action potential durations (APDs) than males. This delayed repolarization results from a lower current density of the ultrarapid delayed rectifier K(+) current (I(K,ur)) and a lower expression level of its underlying K(+) channel (Kv1.5). To evaluate whether this sex difference could be attributable to the action of male sex hormones, we studied the effect of androgen deficiency on ventricular repolarization. We compared cardiac electrophysiological properties in castrated (orchiectomized; ORC) and control (CTL) male mice. Q-Tc intervals as well as APDs measured at 20 %, 50 % and 90 % of repolarization were all significantly longer in ORC than in CTL. The current density of I(K,ur) was significantly lower in ORC than in CTL (at +50 mV, ORC: 29 +/- 4 pA pF(-1), n = 25; CTL: 48 +/- 5 pA pF(-1), n = 17; P = 0.006). In contrast, all the other K(+) currents present in mouse ventricular myocytes were comparable between ORC and CTL. Moreover, results of Western blot analysis showed a lower expression level of Kv1.5 protein in ORC but no difference between the two groups for the other K(+) channels studied. This study demonstrates that androgen deficiency leads to a reduction in the density of I(K,ur) and Kv1.5 in mouse ventricle, and consequently, to prolongation of APD and Q-Tc interval. In conclusion, these findings strongly suggest that male sex hormones contribute to the sex difference that we previously reported in cardiac repolarization in adult mouse heart.
Brouillette
Judith
J
Research Center, Montreal Heart Institute, 5000 Bélanger est, Montréal, Québec, Canada H1T 1C8.
Trépanier-Boulay
Véronique
V
Fiset
Céline
C
D000200:Action Potentials; D000728:Androgens / Q000172:deficiency*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D013196:Dihydrotestosterone / Q000097:blood; D004553:Electric Conductivity; D004562:Electrocardiography; D004594:Electrophysiology; D006706:Homeostasis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009919:Orchiectomy; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011930:Reaction Time; D016276:Ventricular Function
D000728:Androgens; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D013196:Dihydrotestosterone