Aims Pregnant women have a significantly elevated resting heart rate (HR), which makes cardiac arrhythmias more likely to occur. Although electrical remodeling of the sinoatrial node (SAN) has been documented, the underlying mechanism is not fully understood. The acetylcholine-activated potassium current (IKACh), one of the major repolarizing currents in the SAN, plays a critical role in HR control by hyperpolarizing the maximal diastolic potential (MDP) of the SAN action potential (AP), thereby reducing SAN automaticity and HR. Thus, considering its essential role in cardiac automaticity, this study aims to determine whether changes in IKACh are potentially involved in the increased HR associated with pregnancy. Methods and Results Experiments were conducted on non-pregnant (NP, 2-3 months old) and pregnant (P, 17-18 gestation days) female CD-1 mice. IKACh was recorded on spontaneously beating SAN cells using the muscarinic agonist carbachol (CCh). Voltage-clamp data showed a reduction in IKACh density during pregnancy, which returned to control values shortly after delivery. The reduction in IKACh was explained by a decrease in protein expression of Kir3.1 channel subunit and the muscarinic type 2 receptor. In agreement with these findings, current-clamp data shows that the MDP of SAN cells from P mice were less hyperpolarized following CCh administration. Surface electrocardiograms (ECGs) recorded on anesthetized mice revealed that the cholinergic antagonist atropine and the selective KACh channel blocker tertiapin-Q increased HR in NP mice and had only a minimal effect on P mice. AP and ECG data also showed that pregnancy is associated with a decrease in beating and heart rate variability, respectively. Conclusion IKACh function and expression are decreased in the mouse SAN during pregnancy, strongly suggesting that, in addition to other electrical remodeling of the SAN, reduced IKACh also plays an important role in the pregnancy-induced increased HR.

中文翻译：

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妊娠期间窦房结 IKACh 调节心脏自律性


目的 孕妇的静息心率 (HR) 显着升高，这使得心律失常更容易发生。尽管窦房结（SAN）的电重塑已被记录，但其潜在机制尚未完全了解。乙酰胆碱激活钾电流 (IKACh) 是 SAN 中主要的复极电流之一，通过超极化 SAN 动作电位 (AP) 的最大舒张电位 (MDP)，从而降低 SAN 自动性和人力资源。因此，考虑到 IKACh 在心脏自律性中的重要作用，本研究旨在确定 IKACh 的变化是否可能与妊娠相关的 HR 增加有关。方法和结果在未怀孕（NP，2-3 个月大）和怀孕（P，17-18 妊娠天）雌性 CD-1 小鼠上进行实验。使用毒蕈碱激动剂卡巴胆碱 (CCh) 在自发跳动的 SAN 细胞上记录 IKACh。电压钳数据显示怀孕期间 IKACh 密度降低，分娩后不久又恢复到对照值。 IKACh 的减少可以通过 Kir3.1 通道亚基和毒蕈碱 2 型受体的蛋白质表达减少来解释。与这些发现一致的是，电流钳数据显示 P 小鼠 SAN 细胞的 MDP 在 CCh 给药后超极化程度较低。麻醉小鼠的表面心电图 (ECG) 记录显示，胆碱能拮抗剂阿托品和选择性 KACh 通道阻断剂特硫平-Q 增加了 NP 小鼠的心率，而对 P 小鼠的影响很小。 AP 和心电图数据还表明，怀孕分别与心跳和心率变异性的降低有关。 结论 妊娠期间小鼠 SAN 中 IKACh 功能和表达下降，强烈表明，除了 SAN 的其他电重塑之外，IKACh 的减少在妊娠引起的 HR 增加中也发挥着重要作用。