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

Abstract

One of the complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM), whose molecular mechanisms of pathogenesis have not been fully studied. Previously, the involvement of Na⁺/K⁺-ATPase and components of the Ca²⁺ transport system in cardiomyocytes in the development of DCM was shown. The aim of the work was to study the expression and activity of Na⁺/K⁺-ATPase and Ca²⁺-ATPase (SERCA2) in the myocardium of male Wistar rats in a model of streptozotocin (STZ)-induced prediabetes and 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 were considered diabetic (STZ-D1 group), and those with moderate hyperglycemia were considered prediabetic (STZ-preD1 group). The activity of Na⁺/K⁺-ATPase and Ca²⁺-ATPase was determined (by the rate of release of inorganic phosphate, P_i), and the expression of the genes α1- and α2-isoforms of Na⁺/K⁺-ATPase, SERCA2, and Kir6.1, Kv7.1, and Kv2.1 potassium channels was also determined. In the control (C) group, the activity of ouabain (1 mM) -sensitive Mg²⁺-dependent ATPase was 6.03 ± 0.6 mmol Pi/g/h. In the STZ-D1 and STZ-preD1 groups, Na⁺/K⁺-ATPase activity did not differ from group C. The level of gene expression of α1- and α2- subunits of Na⁺/K⁺-ATPase in the STZ-D1 group decreased by more than 45%, then both in the STZ-preD1 group increased by 64 and 81%, which may indicate a high sensitivity of expression to insulinopenia. The activity of Ca²⁺-ATPase and the expression of the SERCA2 gene did not differ between the groups, which might be because the 4-week period after STZ administration is not sufficient for the development of Ca²⁺-ATPase deficiency in the rat heart. The level of expression of the genes of the potassium channel subtypes Kv2.1, Kir6.1, and Kv7.1 increased in the STZ-preD1 group, which may indicate a potential contribution of the studied potassium channel subtypes to the adaptation mechanism to moderate hyperglycemia.