Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart
Abstract Systolic and diastolic dysfunction in diabetes have frequently been associated with abnormal calcium (Ca2+) regulation. However, there is emerging evidence that Ca2+ mishandling alone is insufficient to fully explain diabetic heart dysfunction, with focus shifting to the properties of the m...
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| Format: | Article |
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Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-20520-0 |
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| author | Yann Huey Ng Regis R. Lamberts Peter P. Jones Ivan A. Sammut Gary M. Diffee Gerard T. Wilkins James C. Baldi |
| author_facet | Yann Huey Ng Regis R. Lamberts Peter P. Jones Ivan A. Sammut Gary M. Diffee Gerard T. Wilkins James C. Baldi |
| author_sort | Yann Huey Ng |
| collection | DOAJ |
| description | Abstract Systolic and diastolic dysfunction in diabetes have frequently been associated with abnormal calcium (Ca2+) regulation. However, there is emerging evidence that Ca2+ mishandling alone is insufficient to fully explain diabetic heart dysfunction, with focus shifting to the properties of the myofilament proteins. Our aim was to examine the effects of diabetes on myofilament Ca2+ sensitivity and Ca2+ handling in left ventricular tissues isolated from the same type 2 diabetic rat hearts. We measured the force-pCa relationship in skinned left ventricular cardiomyocytes isolated from 20-week-old type 2 diabetic and non-diabetic rats. Myofilament Ca2+ sensitivity was greater in the diabetic relative to non-diabetic cardiomyocytes, and this corresponded with lower phosphorylation of cardiac troponin I (cTnI) at ser23/24 in the diabetic left ventricular tissues. Protein expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), phosphorylation of phospholamban (PLB) at Ser16, and SERCA/PLB ratio were lower in the diabetic left ventricular tissues. However, the maximum SERCA Ca2+ uptake rate was not different between the diabetic and non-diabetic myocardium. Our data suggest that impaired contractility in the diabetic heart is not caused by SERCA Ca2+ mishandling. This study highlights the important role of the cardiac myofilament and provides new insight on the pathophysiology of diabetic heart dysfunction. |
| first_indexed | 2024-04-11T10:10:53Z |
| format | Article |
| id | doaj.art-969dcf6297a245a9aea8aa4be6b03104 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T10:10:53Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-969dcf6297a245a9aea8aa4be6b031042022-12-22T04:30:06ZengNature PortfolioScientific Reports2045-23222022-10-0112111010.1038/s41598-022-20520-0Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heartYann Huey Ng0Regis R. Lamberts1Peter P. Jones2Ivan A. Sammut3Gary M. Diffee4Gerard T. Wilkins5James C. Baldi6Department of Medicine and HeartOtago, Otago Medical School, University of OtagoDepartment of Physiology and HeartOtago, School of Biomedical Sciences, University of OtagoDepartment of Physiology and HeartOtago, School of Biomedical Sciences, University of OtagoDepartment of Pharmacology and Toxicology and HeartOtago, School of Biomedical Sciences, University of OtagoDepartment of Kinesiology, University of Wisconsin-MadisonDepartment of Medicine and HeartOtago, Otago Medical School, University of OtagoDepartment of Medicine and HeartOtago, Otago Medical School, University of OtagoAbstract Systolic and diastolic dysfunction in diabetes have frequently been associated with abnormal calcium (Ca2+) regulation. However, there is emerging evidence that Ca2+ mishandling alone is insufficient to fully explain diabetic heart dysfunction, with focus shifting to the properties of the myofilament proteins. Our aim was to examine the effects of diabetes on myofilament Ca2+ sensitivity and Ca2+ handling in left ventricular tissues isolated from the same type 2 diabetic rat hearts. We measured the force-pCa relationship in skinned left ventricular cardiomyocytes isolated from 20-week-old type 2 diabetic and non-diabetic rats. Myofilament Ca2+ sensitivity was greater in the diabetic relative to non-diabetic cardiomyocytes, and this corresponded with lower phosphorylation of cardiac troponin I (cTnI) at ser23/24 in the diabetic left ventricular tissues. Protein expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), phosphorylation of phospholamban (PLB) at Ser16, and SERCA/PLB ratio were lower in the diabetic left ventricular tissues. However, the maximum SERCA Ca2+ uptake rate was not different between the diabetic and non-diabetic myocardium. Our data suggest that impaired contractility in the diabetic heart is not caused by SERCA Ca2+ mishandling. This study highlights the important role of the cardiac myofilament and provides new insight on the pathophysiology of diabetic heart dysfunction.https://doi.org/10.1038/s41598-022-20520-0 |
| spellingShingle | Yann Huey Ng Regis R. Lamberts Peter P. Jones Ivan A. Sammut Gary M. Diffee Gerard T. Wilkins James C. Baldi Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart Scientific Reports |
| title | Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart |
| title_full | Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart |
| title_fullStr | Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart |
| title_full_unstemmed | Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart |
| title_short | Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart |
| title_sort | sarco endoplasmic reticulum calcium atpase activity is unchanged despite increased myofilament calcium sensitivity in zucker type 2 diabetic fatty rat heart |
| url | https://doi.org/10.1038/s41598-022-20520-0 |
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