Impaired calcium handling mechanisms in atrial trabeculae of diabetic patients

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.