Aging has different effects on the functional activity and gene expression of classical inward-rectifying potassium channels Kir2.1 and Kir2.4 and ATP-sensitive Katp channels in blood vessels and heart of male rats

Abstract

Aging and related dysregulatory processes in the arteries and heart are the sleading predictors of cardiovascular diseases. Ion channels play an important role in the regulation of vascular and myocardial contractility. The aim of the study was to investigate the effect of age on the functional activity and gene expression of classical inward-rectifying potassium channels Kir2.1 and Kir2.4, as well as K_ATP channels in the aorta and heart of rats. Material and methods. Experiments were performed on Wistar male rats at 3 and 18 months of age. The force of thoracic aorta contractions was measured isometrically, and the gene expression was assessed by PCR analysis. Results. In the aorta of 18-month-old rats, the functional activity of Kir2.1 and Kir2.4 channels was reduced while the expression of these channels remained unchanged. In the aging hearts, on the contrary, the expression level of Kir2.1 and Kir2.4 channel genes was high. The K_ATP channels had no effect on serotonin-induced aortic contractions in young, 3-month-old rats, but contributed significantly to the development of hypersensitivity of aging blood vessels to serotonin-induced vasoconstriction. Thus, blockade of K_ATP channels with glibenclamide led to a significant shift of the concentration-effect curve of serotonin to the right only for the aorta from old rats. Age-related decreases in the gene expression of pore-forming Kir6.2 and regulatory Sur2 subunits of the K_ATP channel were observed in the aorta, and, vice versa, significant increases in their expression were observed in the rat heart. Conclusion. The study results indicated early age-related changes in the functional activity of Kir 2.1 and Kir 2.4 inward-rectifying potassium channels, as well as of K_ATP channels in the aorta of male rat. During further vascular aging, these changes may contribute to the development of hypertension. It was suggested that Kir2.4 and Kir2.1 channel overexpression in the aging heart may initiate disorders of myocardial contractility and arrhythmias in older age. At the same time, a high level of K_ATP subunit expression indicates compensatory-adaptive processes aimed at increasing myocardial resistance to hypoxia and stress.