DEVELOPMENT OF METHOD FOR ANALYSIS OF THE T-TUBULAR SYSTEM IN RAT CARDIOMYOCYTES

The t-system is the highly structured network of membrane invaginations playing an im-portant role in the regulation of cardiac electromechanical coupling and contraction. We de-signed an approach to evaluate the structure of the cardiomyocyte t-tubular system in detail.При поддержке гос.задания ИИФ УрО РАН (тема № AAAA-A19-119070190064-4)

Type 1 Diabetes Impairs Cardiomyocyte Contractility in the Left and Right Ventricular Free Walls but Preserves It in the Interventricular Septum

Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca2+ concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca2+ sensitivity. A decrease in the thin-filament velocity was associated with increased expression of β-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the Russian Science Foundation № 18-74-10059. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology