Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Pregnancy Adaptations

Background:

• Pregnant women exhibit elevated resting heart rate (HR), increasing arrhythmia risk.
• Sinoatrial node (SAN) electrical remodeling is implicated, but mechanisms remain unclear.
• The acetylcholine-activated potassium current (IKACh) is crucial for HR control via SAN action potential regulation.

Purpose of the Study:

• To investigate the role of IKACh in pregnancy-induced increases in heart rate.
• To determine if IKACh function and expression are altered during pregnancy.

Main Methods:

• Electrophysiological recordings (voltage- and current-clamp) of SAN cells from pregnant and non-pregnant mice.
• Measurement of IKACh density and protein expression (Kir3.1, M2 receptor).
• Surface electrocardiograms (ECGs) to assess HR and autonomic modulation.

Main Results:

• IKACh density was reduced in pregnant mice, linked to decreased Kir3.1 and M2 receptor expression.
• Maximal diastolic potential of SAN cells was less hyperpolarized in pregnant mice.
• Pregnancy reduced the HR response to cholinergic agents and decreased heart rate variability.

Conclusions:

• IKACh function and expression are significantly decreased in the mouse SAN during pregnancy.
• Reduced IKACh contributes to the elevated heart rate observed during pregnancy.
• This finding adds to the understanding of SAN electrical remodeling in pregnancy.