| Autor: |
Timothy L. M. Jones, Sarbjot Kaur, Nicholas Kang, Peter N. Ruygrok, Marie‐Louise Ward |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Physiological Reports, Vol 11, Iss 3, Pp n/a-n/a (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2051-817X |
| DOI: |
10.14814/phy2.15599 |
| Popis: |
Abstract The aim of this study was to investigate cardiomyocyte Ca2+ handling and contractile function in freshly excised human atrial tissue from diabetic and non‐diabetic patients undergoing routine surgery. Multicellular trabeculae (283 ± 20 μm in diameter) were dissected from the endocardial surface of freshly obtained right atrial appendage samples from consenting surgical patients. Trabeculae were mounted in a force transducer at optimal length, electrically stimulated to contract, and loaded with fura‐2/AM for intracellular Ca2+ measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca2+ sensitivity was assessed from phase plots and high potassium contractures of force against [Ca2+]i. Trabeculae from diabetic patients (n = 12) had increased diastolic (resting) [Ca2+]i (p = 0.03) and reduced Ca2+ transient amplitude (p = 0.04) when compared to non‐diabetic patients (n = 11), with no difference in the Ca2+ transient time course. Diastolic stress was increased (p = 0.008) in trabeculae from diabetic patients, and peak developed stress decreased (p ≤ 0.001), which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament Ca2+ sensitivity (p = 0.018) compared to non‐diabetic patients. Our data provides evidence of impaired calcium handling during excitation‐contraction coupling with resulting contractile dysfunction in atrial tissue from patients with type 2 diabetes in comparison to the non‐diabetic. This highlights the importance of targeting cardiomyocyte Ca2+ homeostasis in developing more effective treatment options for diabetic heart disease in the future. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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