Study of Na⁺/K⁺-ATPase and Components of the Ca²⁺-Transporting System in Myocardium under Experimental Prediabetes and Type 1 Diabetes in Rats

One of the complications of diabetes mellitus (DM) is diabeticcardiomyopathy (DCM), whose molecular mechanisms of pathogenesishave not been fully studied. Previously, the involvement of Na⁺/K⁺-ATPaseand components of the Ca²⁺ transportsystem in cardiomyocytes in the development of DCM was shown. Theaim of the work was to study the expression and activity of Na⁺/K⁺-ATPaseand Ca²⁺-ATPase (SERCA2) in the myocardiumof male Wistar rats in a model of streptozotocin (STZ)-induced prediabetesand overt type 1 diabetes (T1DM). STZ was administered at once i.p.in doses of 30–35 mg/kg. Rats with glucose levels above 11 mM wereconsidered diabetic (STZ-D1 group), and those with moderate hyperglycemiawere considered prediabetic (STZ-preD1 group). The activity of Na⁺/K⁺-ATPaseand Ca²⁺-ATPase was determined (by therate of release of inorganic phosphate, P_i), andthe expression of the genes α1- and α2-isoforms of Na⁺/K⁺-ATPase,SERCA2, and Kir6.1, Kv7.1, and Kv2.1 potassium channels was alsodetermined. In the control (C) group, the activity of ouabain (1 mM)-sensitive Mg²⁺-dependent ATPase was6.03 ± 0.6 mmol Pi/g/h. In the STZ-D1 and STZ-preD1 groups, Na⁺/K⁺-ATPaseactivity did not differ from group C. The level of gene expressionof α1- and α2- subunits of Na⁺/K⁺-ATPasein the STZ-D1 group decreased by more than 45%, then both in theSTZ-preD1 group increased by 64 and 81%, which may indicate a highsensitivity of expression to insulinopenia. The activity of Ca²⁺-ATPaseand the expression of the SERCA2 gene did not differ between thegroups, which might be because the 4-week period after STZ administrationis not sufficient for the development of Ca²⁺-ATPasedeficiency in the rat heart. The level of expression of the genesof the potassium channel subtypes Kv2.1, Kir6.1, and Kv7.1 increasedin the STZ-preD1 group, which may indicate a potential contributionof the studied potassium channel subtypes to the adaptation mechanism tomoderate hyperglycemia.