Influence of miR-221/222 on cardiomyocyte calcium handling and function
Abstract Background Cardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 ar...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-021-00676-4 |
| _version_ | 1819124955535638528 |
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| author | Maria Knyrim Sindy Rabe Claudia Grossmann Michael Gekle Barbara Schreier |
| author_facet | Maria Knyrim Sindy Rabe Claudia Grossmann Michael Gekle Barbara Schreier |
| author_sort | Maria Knyrim |
| collection | DOAJ |
| description | Abstract Background Cardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 are involved in structural remodeling, their role in electrical remodeling still has to be evaluated. We previously reported that subunits of the L-type Ca2+ channel (LTCC) are direct targets of miR-221/222. Furthermore, HL-1 cells transfected with miR-221 or -222 mimics showed a reduction in LTCC current density while the voltage-dependence of activation was not altered. The aim of the present study was to determine the influence of miR-221/222 on cardiomyocyte calcium handling and function. Results Transient transfection of HL-1 cells with miR-221/222 mimics led to slower depolarization-dependent Ca2+ entry and increased proportion of non-responding cells. Angiotensin II-induced Ca2+ release from the SR was not affected by miR-221/222. In miR-222-transfected neonatal cardiomyocytes the isoprenaline-induced positive inotropic effect on the intracellular Ca2+ transient was lost and the positive chronotropic effect on spontaneous beating activity was strongly reduced. This could have severe consequences for cardiomyocytes and could lead to a reduced contractility and systolic dysfunction of the whole heart. Conclusions This study adds a new role of miR-221/222 in cardiomyocytes by showing the impact on β-adrenergic regulation of LTCC function, calcium handling and beating frequency. Together with the previous report that miR-221/222 reduce GIRK1/4 function and LTCC current density, it expands our knowledge about the role of these miRs on cardiac ion channel regulation. |
| first_indexed | 2024-12-22T07:32:28Z |
| format | Article |
| id | doaj.art-78d3075246294c98ab957cbd4f148eb3 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-22T07:32:28Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-78d3075246294c98ab957cbd4f148eb32022-12-21T18:33:59ZengBMCCell & Bioscience2045-37012021-08-0111111610.1186/s13578-021-00676-4Influence of miR-221/222 on cardiomyocyte calcium handling and functionMaria Knyrim0Sindy Rabe1Claudia Grossmann2Michael Gekle3Barbara Schreier4Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-WittenbergJulius-Bernstein-Institute of Physiology, Martin Luther University Halle-WittenbergJulius-Bernstein-Institute of Physiology, Martin Luther University Halle-WittenbergJulius-Bernstein-Institute of Physiology, Martin Luther University Halle-WittenbergJulius-Bernstein-Institute of Physiology, Martin Luther University Halle-WittenbergAbstract Background Cardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 are involved in structural remodeling, their role in electrical remodeling still has to be evaluated. We previously reported that subunits of the L-type Ca2+ channel (LTCC) are direct targets of miR-221/222. Furthermore, HL-1 cells transfected with miR-221 or -222 mimics showed a reduction in LTCC current density while the voltage-dependence of activation was not altered. The aim of the present study was to determine the influence of miR-221/222 on cardiomyocyte calcium handling and function. Results Transient transfection of HL-1 cells with miR-221/222 mimics led to slower depolarization-dependent Ca2+ entry and increased proportion of non-responding cells. Angiotensin II-induced Ca2+ release from the SR was not affected by miR-221/222. In miR-222-transfected neonatal cardiomyocytes the isoprenaline-induced positive inotropic effect on the intracellular Ca2+ transient was lost and the positive chronotropic effect on spontaneous beating activity was strongly reduced. This could have severe consequences for cardiomyocytes and could lead to a reduced contractility and systolic dysfunction of the whole heart. Conclusions This study adds a new role of miR-221/222 in cardiomyocytes by showing the impact on β-adrenergic regulation of LTCC function, calcium handling and beating frequency. Together with the previous report that miR-221/222 reduce GIRK1/4 function and LTCC current density, it expands our knowledge about the role of these miRs on cardiac ion channel regulation.https://doi.org/10.1186/s13578-021-00676-4miR-221/222CardiomyocytesRemodelingL-type Ca2+ channel |
| spellingShingle | Maria Knyrim Sindy Rabe Claudia Grossmann Michael Gekle Barbara Schreier Influence of miR-221/222 on cardiomyocyte calcium handling and function Cell & Bioscience miR-221/222 Cardiomyocytes Remodeling L-type Ca2+ channel |
| title | Influence of miR-221/222 on cardiomyocyte calcium handling and function |
| title_full | Influence of miR-221/222 on cardiomyocyte calcium handling and function |
| title_fullStr | Influence of miR-221/222 on cardiomyocyte calcium handling and function |
| title_full_unstemmed | Influence of miR-221/222 on cardiomyocyte calcium handling and function |
| title_short | Influence of miR-221/222 on cardiomyocyte calcium handling and function |
| title_sort | influence of mir 221 222 on cardiomyocyte calcium handling and function |
| topic | miR-221/222 Cardiomyocytes Remodeling L-type Ca2+ channel |
| url | https://doi.org/10.1186/s13578-021-00676-4 |
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