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 ß-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.

Differing effects of estrogen deficiency on the contractile function of atrial and ventricular myocardium.

Estrogen deficiency has a significant influence on the excitation-contraction coupling in the ventricular myocardium but its impact on the atrial contractile function has not been studied. We have compared the effects of estrogen deficiency on the contractility and cytosolic Ca2+ transient of single cardiomyocytes isolated from the left atrium (LA) and the left ventricle (LV) of rats subjected to ovariectomy (OVX) or sham surgery (Sham). The characteristics of actin-myosin interaction were studied in an in vitro motility assay. We found that OVX decreased the contractility of LV single cardiomyocytes but increased that of LA myocytes. The disturbance of ventricular mechanical function may be explained by the acceleration of Ca2+ transient and reduced Ca2+ sensitivity of the actin-myosin interaction. The augmentation of LA contractility may be explained by accelerated cross-bridge kinetics and increased end-diastolic sarcomere length, which may lead to elevated tension in atrial cells due to the Frank-Starling mechanism.