Integrative Physiology Estrogen Contributes to Gender Differences in Mouse Ventricular Repolarization
نویسندگان
چکیده
Rationale: Fast-transient outward K (Ito,f) and ultrarapid delayed rectifier K currents (IK,slow, also known as IKur) contribute to mouse cardiac repolarization. Gender studies on these currents have reported conflicting results. Objective: Key missing information in these studies is the estral stage of the animals. We revisited gender-related differences in K currents, taking into consideration the females’ estral stage. We hypothesized that changes in estrogen levels during the estral cycle could play a role in determining the densities of K currents underlying ventricular repolarization. Methods and Results: Peak total K current (IK,total) densities (pA/pF, at 40 mV) were much higher in males (48.6 3.0) versus females at estrus (27.2 2.3) but not at diestrus-2 (39.1 3.4). Underlying this change, Ito,f and IK,slow were lower in females at estrus versus males and diestrus-2 (IK,slow: male 21.9 1.8, estrus 14.6 0.6, diestrus-2 20.3 1.4; Ito,f: male 26.8 1.9, estrus 14.9 1.6, diestrus-2 22.1 2.1). Lower IK,slow in estrus was attributable to only IK,slow1 reduction, without changes in IK,slow2. Estrogen treatment of ovariectomized mice decreased IK,total (46.4 3.0 to 28.4 1.6), Ito,f (26.6 1.6 to 12.8 1.0) and IK,slow (22.2 1.6 to 17.2 1.4). Transcript levels of Kv4.3 and Kv1.5 (underlying Ito,f and IK,slow, respectively) were lower in estrus versus diestrus-2 and male. In ovariectomized mice, estrogen treatment resulted in downregulation of Kv4.3 and Kv1.5 but not Kv4.2, KChIP2, or Kv2.1 transcripts. K current reduction in high estrogenic conditions were associated with prolongation of the action potential duration and corrected QT interval. Conclusion: Downregulation of Kv4.3 and Kv1.5 transcripts by estrogen are one mechanism defining gender-related differences in mouse ventricular repolarization. (Circ Res. 2009;105:343-352.)
منابع مشابه
Estrogen contributes to gender differences in mouse ventricular repolarization.
RATIONALE Fast-transient outward K(+) (I(to,f)) and ultrarapid delayed rectifier K(+) currents (I(K,slow), also known as I(Kur)) contribute to mouse cardiac repolarization. Gender studies on these currents have reported conflicting results. OBJECTIVE Key missing information in these studies is the estral stage of the animals. We revisited gender-related differences in K(+) currents, taking in...
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