Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes
Introduction: In ventricular myocytes, spontaneous release of calcium (Ca2+) from the sarcoplasmic reticulum via ryanodine receptors (“Ca2+ sparks”) is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of isc...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-04-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00289/full |
| _version_ | 1830343487975849984 |
|---|---|
| author | Breanne A. Cameron Hiroaki Kai Keiko Kaihara Gentaro Iribe Gentaro Iribe T. Alexander Quinn T. Alexander Quinn |
| author_facet | Breanne A. Cameron Hiroaki Kai Keiko Kaihara Gentaro Iribe Gentaro Iribe T. Alexander Quinn T. Alexander Quinn |
| author_sort | Breanne A. Cameron |
| collection | DOAJ |
| description | Introduction: In ventricular myocytes, spontaneous release of calcium (Ca2+) from the sarcoplasmic reticulum via ryanodine receptors (“Ca2+ sparks”) is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of ischemic tissue, along with an increase in Ca2+ spark rate and ROS production, each of which has been implicated in arrhythmogenesis. Yet, whether there is an impact of ischemia on the stretch-induced increase in Ca2+ sparks and ROS has not been investigated. We hypothesized that ischemia would enhance the increase of Ca2+ sparks and ROS that occurs with stretch.Methods: Isolated ventricular myocytes from mice (male, C57BL/6J) were loaded with fluorescent dye to detect Ca2+ sparks (4.6 μM Fluo-4, 10 min) or ROS (1 μM DCF, 20 min), exposed to normal Tyrode (NT) or simulated ischemia (SI) solution (hyperkalemia [15 mM potassium], acidosis [6.5 pH], and metabolic inhibition [1 mM sodium cyanide, 20 mM 2-deoxyglucose]), and subjected to sustained stretch by the carbon fiber technique (~10% increase in sarcomere length, 15 s). Ca2+ spark rate and rate of ROS production were measured by confocal microscopy.Results: Baseline Ca2+ spark rate was greater in SI (2.54 ± 0.11 sparks·s−1·100 μm−2; n = 103 cells, N = 10 mice) than NT (0.29 ± 0.05 sparks·s−1·100 μm−2; n = 33 cells, N = 9 mice; p < 0.0001). Stretch resulted in an acute increase in Ca2+ spark rate in both SI (3.03 ± 0.13 sparks·s−1·100 μm−2; p < 0.0001) and NT (0.49 ± 0.07 sparks·s−1·100 μm−2; p < 0.0001), with the increase in SI being greater than NT (+0.49 ± 0.04 vs. +0.20 ± 0.04 sparks·s−1·100 μm−2; p < 0.0001). Baseline rate of ROS production was also greater in SI (1.01 ± 0.01 normalized slope; n = 11, N = 8 mice) than NT (0.98 ± 0.01 normalized slope; n = 12, N = 4 mice; p < 0.05), but there was an acute increase with stretch only in SI (+12.5 ± 2.6%; p < 0.001).Conclusion: Ischemia enhances the stretch-induced increase of Ca2+ sparks in ventricular myocytes, with an associated enhancement of stretch-induced ROS production. This effect may be important for premature excitation and/or in the development of an arrhythmogenic substrate in acute regional ischemia. |
| first_indexed | 2024-12-19T22:10:14Z |
| format | Article |
| id | doaj.art-fc1c2a7d08cd4719a1e0cea463ff6f5f |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T22:10:14Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-fc1c2a7d08cd4719a1e0cea463ff6f5f2022-12-21T20:03:57ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-04-011110.3389/fphys.2020.00289504103Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular MyocytesBreanne A. Cameron0Hiroaki Kai1Keiko Kaihara2Gentaro Iribe3Gentaro Iribe4T. Alexander Quinn5T. Alexander Quinn6Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, CanadaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, JapanGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, JapanGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, JapanDepartment of Physiology, Asahikawa Medical University, Asahikawa, JapanDepartment of Physiology and Biophysics, Dalhousie University, Halifax, NS, CanadaSchool of Biomedical Engineering, Dalhousie University, Halifax, NS, CanadaIntroduction: In ventricular myocytes, spontaneous release of calcium (Ca2+) from the sarcoplasmic reticulum via ryanodine receptors (“Ca2+ sparks”) is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of ischemic tissue, along with an increase in Ca2+ spark rate and ROS production, each of which has been implicated in arrhythmogenesis. Yet, whether there is an impact of ischemia on the stretch-induced increase in Ca2+ sparks and ROS has not been investigated. We hypothesized that ischemia would enhance the increase of Ca2+ sparks and ROS that occurs with stretch.Methods: Isolated ventricular myocytes from mice (male, C57BL/6J) were loaded with fluorescent dye to detect Ca2+ sparks (4.6 μM Fluo-4, 10 min) or ROS (1 μM DCF, 20 min), exposed to normal Tyrode (NT) or simulated ischemia (SI) solution (hyperkalemia [15 mM potassium], acidosis [6.5 pH], and metabolic inhibition [1 mM sodium cyanide, 20 mM 2-deoxyglucose]), and subjected to sustained stretch by the carbon fiber technique (~10% increase in sarcomere length, 15 s). Ca2+ spark rate and rate of ROS production were measured by confocal microscopy.Results: Baseline Ca2+ spark rate was greater in SI (2.54 ± 0.11 sparks·s−1·100 μm−2; n = 103 cells, N = 10 mice) than NT (0.29 ± 0.05 sparks·s−1·100 μm−2; n = 33 cells, N = 9 mice; p < 0.0001). Stretch resulted in an acute increase in Ca2+ spark rate in both SI (3.03 ± 0.13 sparks·s−1·100 μm−2; p < 0.0001) and NT (0.49 ± 0.07 sparks·s−1·100 μm−2; p < 0.0001), with the increase in SI being greater than NT (+0.49 ± 0.04 vs. +0.20 ± 0.04 sparks·s−1·100 μm−2; p < 0.0001). Baseline rate of ROS production was also greater in SI (1.01 ± 0.01 normalized slope; n = 11, N = 8 mice) than NT (0.98 ± 0.01 normalized slope; n = 12, N = 4 mice; p < 0.05), but there was an acute increase with stretch only in SI (+12.5 ± 2.6%; p < 0.001).Conclusion: Ischemia enhances the stretch-induced increase of Ca2+ sparks in ventricular myocytes, with an associated enhancement of stretch-induced ROS production. This effect may be important for premature excitation and/or in the development of an arrhythmogenic substrate in acute regional ischemia.https://www.frontiersin.org/article/10.3389/fphys.2020.00289/fullcalciumischemiamyocytesreactive oxygen speciesstretchventricle |
| spellingShingle | Breanne A. Cameron Hiroaki Kai Keiko Kaihara Gentaro Iribe Gentaro Iribe T. Alexander Quinn T. Alexander Quinn Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes Frontiers in Physiology calcium ischemia myocytes reactive oxygen species stretch ventricle |
| title | Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes |
| title_full | Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes |
| title_fullStr | Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes |
| title_full_unstemmed | Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes |
| title_short | Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes |
| title_sort | ischemia enhances the acute stretch induced increase in calcium spark rate in ventricular myocytes |
| topic | calcium ischemia myocytes reactive oxygen species stretch ventricle |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00289/full |
| work_keys_str_mv | AT breanneacameron ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT hiroakikai ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT keikokaihara ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT gentaroiribe ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT gentaroiribe ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT talexanderquinn ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes AT talexanderquinn ischemiaenhancestheacutestretchinducedincreaseincalciumsparkrateinventricularmyocytes |