Changes in Contractile Function of Single Cardiomyocytes from the Different Heart Chambers in Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2D) is a leading cause of cardiovascular disease. Cardiomyocyte contractile function and excitation-contraction coupling in different heart chambers are still poorly understood. This work aimed to study the changes in parameters of sarcomere shortening and cytosolic free Ca2+ transient of single cardiomyocytes from the left and right ventricular free walls (LV, RV), the left and right atria (LA, RA), and the interventricular septum (S) in T2D.The study was conducted on Wistar rats in accordance with the Directive 2010/63/EU. T2D was induced by streptozotocin (65 mg/kg, i.p.) following nicotinamide administration (110 mg/kg i.p.). Single cardiomyocytes were obtained using the Langendorff technique with modifications (Butova et al., 2020). For [Ca2+]i measurements cardiomyocytes were loaded with the Ca2+ indicator Fluo-8AM. Experiments were carried out at stimulation frequencies of 0.5, 1, 2 and 3 Hz at 36 - 37ºC.End-diastolic sarcomere length was not significantly affected by T2D in any of cardiac chambers. In T2D rats, the sarcomere shortening amplitudes were greater in LA, RV, and S, but remained unchanged in RA and LV compared with the control group. The amplitudes of Ca2+ transients were smaller in the right heart chambers, however were higher in the left heart chambers and unchanged in S in T2D rats. T2D prolonged the time course of Ca2+ transient and sarcomere shortening in ventricles and S, but not in atria. In rats with T2D, we found a significant increase in the frequency of Ca2+ sparks in S, while no significant changes were observed in other chambers.Thus, the cardiac remodeling in T2D manifests itself with specific features of changes in contractile function between the different heart chambers.Supported by The Russian Science Foundation (# 18-74-10059).