Impaired calcium handling mechanisms in atrial trabeculae of diabetic patients. Issue 3 (7th February 2023)

• Record Type: Journal Article
• Authors: Jones, Timothy L. M.; Kaur, Sarbjot; Kang, Nicholas; Ruygrok, Peter N.; Ward, Marie‐Louise
• Is Part Of: Physiological reports. Volume 11:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-07
• Subjects: calcium handling -- diabetes -- human right atrial trabeculae -- myofilament sensitivity; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.15599
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: The aim of this study was to investigate cardiomyocyte Ca 2+ 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 Ca 2+ measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca 2+ sensitivity was assessed from phase plots and high potassium contractures of force against [Ca 2+ ]i . Trabeculae from diabetic patients ( n = 12) had increased diastolic (resting) [Ca 2+ ]i ( p = 0.03) and reduced Ca 2+ transient amplitude ( p = 0.04) when compared to non‐diabetic patients ( n = 11), with no difference in the Ca 2+ 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 Ca 2+ 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 Ca 2+ homeostasis in developing more effective treatment options for diabetic heart disease in the future. Abstract : The aim of this study was to investigate cardiomyocyte calcium and contractile function in freshly excised human atrial tissue from consenting diabetic and non‐diabetic patients. Trabeculae from diabetic patients ( n = 12) had increased diastolic (resting) calcium and reduced calcium transient amplitude compared to trabeculae from non‐diabetic patients ( n = 11), with no difference in the transient time course. Diastolic stress was increased in trabeculae from diabetic patients, and peak developed stress decreased, which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament calcium sensitivity. 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.