Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids
Summary: Protein kinase A (PKA) phosphorylates proteins crucial for rhythm modulation, with its dysregulation linked to arrhythmias. This study investigated PKA activity’s spatiotemporal dynamics in spontaneously beating cardiac organoids. We hypothesized that PKA activity would respond to autonomic...
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225002652 |
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| author | Ido Weiser-Bitoun Savyon Mazgaoker Rami Eid Inbar Brosh Yael Yaniv |
| author_facet | Ido Weiser-Bitoun Savyon Mazgaoker Rami Eid Inbar Brosh Yael Yaniv |
| author_sort | Ido Weiser-Bitoun |
| collection | DOAJ |
| description | Summary: Protein kinase A (PKA) phosphorylates proteins crucial for rhythm modulation, with its dysregulation linked to arrhythmias. This study investigated PKA activity’s spatiotemporal dynamics in spontaneously beating cardiac organoids. We hypothesized that PKA activity would respond to autonomic stimulation and exhibit spatial heterogeneity upon drug-induced modulation. Forskolin (activator) and H-89 (inhibitor) altered PKA activity ratios from 1 to 1.52 ± 0.03 and 0.89 ± 0.03, respectively. Hill equation-based regression showed a high fit of PKA activity behavior for all four tested drugs (forskolin, H-89, isoproterenol, or carbachol) at concentrations. Responses to forskolin or isoproterenol, which increase PKA activity, showed higher heterogeneity (10.1 ± 0.8% or 8.7 ± 1%) compared to responses to H-89 or carbachol (4.3 ± 0.8% or 4.4 ± 1.2%), which decrease PKA activity. These results reveal the intricate spatial dynamics of PKA activity in cardiac organoids and its dependence on PKA activation levels. |
| format | Article |
| id | doaj-art-d193a5d6f95547c2bae0cd00fd2d1edd |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-d193a5d6f95547c2bae0cd00fd2d1edd2025-08-20T02:03:46ZengElsevieriScience2589-00422025-03-0128311200510.1016/j.isci.2025.112005Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoidsIdo Weiser-Bitoun0Savyon Mazgaoker1Rami Eid2Inbar Brosh3Yael Yaniv4Laboratory of Bioelectric and Bioenergetic Systems, Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3525433, Israel; Department of Internal Medicine “C”, Rambam Health Care Campus, Haifa 3109601, IsraelLaboratory of Bioelectric and Bioenergetic Systems, Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, IsraelLaboratory of Bioelectric and Bioenergetic Systems, Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, IsraelLaboratory of Bioelectric and Bioenergetic Systems, Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, IsraelLaboratory of Bioelectric and Bioenergetic Systems, Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel; Corresponding authorSummary: Protein kinase A (PKA) phosphorylates proteins crucial for rhythm modulation, with its dysregulation linked to arrhythmias. This study investigated PKA activity’s spatiotemporal dynamics in spontaneously beating cardiac organoids. We hypothesized that PKA activity would respond to autonomic stimulation and exhibit spatial heterogeneity upon drug-induced modulation. Forskolin (activator) and H-89 (inhibitor) altered PKA activity ratios from 1 to 1.52 ± 0.03 and 0.89 ± 0.03, respectively. Hill equation-based regression showed a high fit of PKA activity behavior for all four tested drugs (forskolin, H-89, isoproterenol, or carbachol) at concentrations. Responses to forskolin or isoproterenol, which increase PKA activity, showed higher heterogeneity (10.1 ± 0.8% or 8.7 ± 1%) compared to responses to H-89 or carbachol (4.3 ± 0.8% or 4.4 ± 1.2%), which decrease PKA activity. These results reveal the intricate spatial dynamics of PKA activity in cardiac organoids and its dependence on PKA activation levels.http://www.sciencedirect.com/science/article/pii/S2589004225002652Natural sciencesBiological sciencesCell biologyStem cells research |
| spellingShingle | Ido Weiser-Bitoun Savyon Mazgaoker Rami Eid Inbar Brosh Yael Yaniv Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids iScience Natural sciences Biological sciences Cell biology Stem cells research |
| title | Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids |
| title_full | Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids |
| title_fullStr | Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids |
| title_full_unstemmed | Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids |
| title_short | Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids |
| title_sort | spatiotemporal profiling of protein kinase a activity in spontaneously beating hipsc derived cardiac organoids |
| topic | Natural sciences Biological sciences Cell biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225002652 |
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