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.

17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca²⁺]_i transients were measured in mechanically non-loaded CM, and the tension–length relationship was studied in CM mechanically loaded by carbon fibers. The actin–myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca²⁺]_i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension–length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT.

The study of cardiac function is important issue in physiological and biological sciences and has relevant implications for clinical practice. The interpretation of the whole-heart experiments is complicated by multi-cellular interactions. This work is devoted to the development of biomechanical tests for studying force-length and passive viscoelastic properties of intact single cardiac muscle cells using a glue-free carbon fiber technique. The developed tests allow analyzing the passive force-length, total force-length and active force-length relations in a beating cardiomyocyte by applying the step stretch protocol. The protocols also can be used to investigate in detail the viscoelastic hysteresis applying sawtooth stretch and release commands on a resting cell. The tracking of viscoelastic hysteresis allows one to study not only changes in the passive tension amplitude, but also the delay between the micromanipulator movement and the cell response or energy dissipation specifying viscoelastic properties. Thus, the developed biomechanical tests are powerful research tools to study cardiac biomechanics at the cell level.