Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling
Males and females differ in the basic anatomy and physiology of the heart. Sex differences are evident in cardiac repolarization in humans; women have longer corrected QT and JT intervals. However, the molecular mechanisms that lead to these differences are incompletely understood. Here, we present...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/10/12/479 |
| _version_ | 1797380594752028672 |
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| author | James I. Emerson Pablo Ariel Wei Shi Frank L. Conlon |
| author_facet | James I. Emerson Pablo Ariel Wei Shi Frank L. Conlon |
| author_sort | James I. Emerson |
| collection | DOAJ |
| description | Males and females differ in the basic anatomy and physiology of the heart. Sex differences are evident in cardiac repolarization in humans; women have longer corrected QT and JT intervals. However, the molecular mechanisms that lead to these differences are incompletely understood. Here, we present that, like in humans, sex differences in QT and JT intervals exist in mouse models; female mice had longer corrected QT and JT intervals compared with age-matched males. To further understand the molecular underpinning of these sex differences, we developed a novel technology using fluorescent confocal microscopy that allows the simultaneous visualization of action potential, Ca<sup>2+</sup> transients, and contractions in isolated cardiomyocytes at a high temporal resolution. From this approach, we uncovered that females at baseline have increased action potential duration, decreased Ca<sup>2+</sup> release and reuptake rates, and decreased contraction and relaxation velocities compared with males. Additionally, males had a shorter overall time from action potential onset to peak contraction. In aggregate, our studies uncovered male and female differences in excitation-contraction coupling that account for differences observed in the EKG. Overall, a better understanding of sex differences in electrophysiology is essential for equitably treating cardiac disease. |
| first_indexed | 2024-03-08T20:39:35Z |
| format | Article |
| id | doaj.art-264bbcbee44b4c5294b835aa5c3de4aa |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-08T20:39:35Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-264bbcbee44b4c5294b835aa5c3de4aa2023-12-22T14:16:41ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252023-11-01101247910.3390/jcdd10120479Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction CouplingJames I. Emerson0Pablo Ariel1Wei Shi2Frank L. Conlon3Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMicroscopy Services Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biology and Genetics, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Biology and Genetics, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMales and females differ in the basic anatomy and physiology of the heart. Sex differences are evident in cardiac repolarization in humans; women have longer corrected QT and JT intervals. However, the molecular mechanisms that lead to these differences are incompletely understood. Here, we present that, like in humans, sex differences in QT and JT intervals exist in mouse models; female mice had longer corrected QT and JT intervals compared with age-matched males. To further understand the molecular underpinning of these sex differences, we developed a novel technology using fluorescent confocal microscopy that allows the simultaneous visualization of action potential, Ca<sup>2+</sup> transients, and contractions in isolated cardiomyocytes at a high temporal resolution. From this approach, we uncovered that females at baseline have increased action potential duration, decreased Ca<sup>2+</sup> release and reuptake rates, and decreased contraction and relaxation velocities compared with males. Additionally, males had a shorter overall time from action potential onset to peak contraction. In aggregate, our studies uncovered male and female differences in excitation-contraction coupling that account for differences observed in the EKG. Overall, a better understanding of sex differences in electrophysiology is essential for equitably treating cardiac disease.https://www.mdpi.com/2308-3425/10/12/479sex differencescardiac electrophysiologyexcitation-contraction coupling |
| spellingShingle | James I. Emerson Pablo Ariel Wei Shi Frank L. Conlon Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling Journal of Cardiovascular Development and Disease sex differences cardiac electrophysiology excitation-contraction coupling |
| title | Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling |
| title_full | Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling |
| title_fullStr | Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling |
| title_full_unstemmed | Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling |
| title_short | Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling |
| title_sort | sex differences in mouse cardiac electrophysiology revealed by simultaneous imaging of excitation contraction coupling |
| topic | sex differences cardiac electrophysiology excitation-contraction coupling |
| url | https://www.mdpi.com/2308-3425/10/12/479 |
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