Effect of androgen deficiency on mouse ventricular repolarization

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Cardiology

Background:

• Female mouse ventricles exhibit longer action potential durations (APDs) than males.
• This sex difference is linked to lower ultrarapid delayed rectifier potassium current (I(K,ur)) density and Kv1.5 channel expression in females.
• The role of male sex hormones in cardiac repolarization remains to be fully elucidated.

Purpose of the Study:

• To investigate the impact of androgen deficiency on ventricular repolarization in male mice.
• To determine if male sex hormones influence the ultrarapid delayed rectifier K(+) current (I(K,ur)) and its underlying Kv1.5 channel.

Main Methods:

• Comparison of cardiac electrophysiological properties between castrated (orchiectomized; ORC) and control (CTL) male mice.
• Measurement of Q-Tc intervals and action potential durations (APDs) at various repolarization points.
• Assessment of I(K,ur) current density using patch-clamp electrophysiology.
• Quantification of Kv1.5 and other K(+) channel expression levels via Western blot analysis.

Main Results:

• Orchiectomized (ORC) male mice showed significantly longer Q-Tc intervals and APDs compared to control (CTL) mice.
• I(K,ur) current density was significantly lower in ORC mice (29 ± 4 pA/pF) than in CTL mice (48 ± 5 pA/pF) at +50 mV.
• Kv1.5 protein expression was reduced in ORC mice, while other K(+) channel expressions remained comparable between groups.

Conclusions:

• Androgen deficiency in male mice leads to reduced I(K,ur) density and Kv1.5 expression in the ventricle.
• This hormonal imbalance results in prolonged ventricular action potential duration and Q-Tc interval.
• Male sex hormones play a significant role in establishing sex differences in cardiac repolarization.