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Scientific article
English

Upregulation of the hyperpolarization-activated current increases pacemaker activity of the sinoatrial node and heart rate during pregnancy in mice

Published inCirculation, vol. 127, no. 20, p. 2009-2020
Publication date2013-05-21
First online date2013-04-22
Abstract

Background: Pregnancy is associated with a faster heart rate (HR), which is a risk factor for arrhythmias. However, the underlying mechanisms for this increased HR are poorly understood. Therefore, this study was performed to gain mechanistic insight into the pregnancy-induced increase in HR.

Methods and results: Using surface ECG we observed that pregnant (P) mice have faster HR (531±14 beats per minute [bpm]) compared with nonpregnant (NP) mice (470±27 bpm; P<0.03). Results obtained with Langendorff-perfused hearts showed that this difference persisted in the absence of autonomic nervous innervation (NP, 327±16 bpm; P, 385±18 bpm; P<0.02). Spontaneous action potentials of sinoatrial node cells from pregnant mice exhibited higher automaticity (NP, 292±13 bpm; P, 330±12 bpm; P=0.047) and steeper diastolic depolarization (NP, 0.20±0.03 V/s; P, 0.40±0.06 V/s; P=0.004). Pregnancy increased the density of the hyperpolarization-activated current (If) (at -90mV: NP, -15.2±1.0 pA/pF; P, -28.6±2.9 pA/pF; P=0.0002) in sinoatrial node cells. Voltage dependence of the If activation curve and the intracellular cAMP levels were unchanged in sinoatrial node cells of pregnant mice. However, there was a significant increase in HCN2 channel protein expression with no change in HCN4 expression. Maximal depolarizing shift of the If activation curve induced by isoproterenol was attenuated in pregnancy. This reduced response to isoproterenol may be attributable to the lower cAMP sensitivity of HCN2 isoform compared with that of HCN4.

Conclusions: This study shows that an increase in If current density contributes to the acceleration of sinoatrial node automaticity and explains, in part, the higher HR observed in pregnancy.

eng
Keywords
  • Heart rate
  • Ion channels
  • Pacemakers, biological
  • Pregnancy
  • Sinoatrial node
  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / biosynthesis
  • Female
  • Heart Conduction System / physiology
  • Heart Rate / physiology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / biosynthesis
  • Mice
  • Potassium Channels
  • Pregnancy / physiology
  • Sinoatrial Node / physiology
  • Up-Regulation / physiology
Affiliation Not a UNIGE publication
Citation (ISO format)
EL KHOURY, Nabil et al. Upregulation of the hyperpolarization-activated current increases pacemaker activity of the sinoatrial node and heart rate during pregnancy in mice. In: Circulation, 2013, vol. 127, n° 20, p. 2009–2020. doi: 10.1161/CIRCULATIONAHA.113.001689
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Article (Published version)
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ISSN of the journal0009-7322
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