| First Author | Long V | Year | 2020 |
| Journal | J Mol Cell Cardiol | Volume | 147 |
| Pages | 27-34 | PubMed ID | 32798536 |
| Mgi Jnum | J:296011 | Mgi Id | MGI:6455623 |
| Doi | 10.1016/j.yjmcc.2020.08.005 | Citation | Long V, et al. (2020) Contribution of estrogen to the pregnancy-induced increase in cardiac automaticity. J Mol Cell Cardiol 147:27-34 |
| abstractText | BACKGROUND: The heart rate progressively increases throughout pregnancy, reaching a maximum in the third trimester. This elevated heart rate is also present in pregnant mice and is associated with accelerated automaticity, higher density of the pacemaker current If and changes in Ca(2+) homeostasis in sinoatrial node (SAN) cells. Strong evidence has also been provided showing that 17beta-estradiol (E2) and estrogen receptor alpha (ERalpha) regulate heart rate. Accordingly, we sought to determine whether E2 levels found in late pregnancy cause the increased cardiac automaticity associated with pregnancy. METHODS AND RESULTS: Voltage- and current-clamp experiments were carried out on SAN cells isolated from female mice lacking estrogen receptor alpha (ERKOalpha) or beta (ERKObeta) receiving chronic E2 treatment mimicking late pregnancy concentrations. E2 treatment significantly increased the action potential rate (284 +/- 24 bpm, +E2 354 +/- 23 bpm, p = 0.040) and the density of If (+52%) in SAN cells from ERKObeta mice. However, If density remains unchanged in SAN cells from E2-treated ERKOalpha mice. Additionally, E2 also increased If density (+67%) in nodal-like human-induced pluripotent stem cell-derived cardiomyocytes (N-hiPSC-CM), recapitulating in a human SAN cell model the effect produced in mice. However, the L-type calcium current (ICaL) and Ca(2+) transients, examined using N-hiPSC-CM and SAN cells respectively, were not affected by E2, indicating that other mechanisms contribute to changes observed in these parameters during pregnancy. CONCLUSION: The accelerated SAN automaticity observed in E2-treated ERKObeta mice is explained by an increased If density mediated by ERalpha, demonstrating that E2 plays a major role in regulating SAN function during pregnancy. |
