Changes in expression of mitochondrial ATP-sensitive potassium channels and mitochondrial function in the hearts of mice with heart failure related to diabetic cardiomyopathy
WANG Jinxin
CHENG Xiaowei
ZHU Zifan
MA Jinling
WANG Haijun
ZHU Qinglei
LIU Hongbin
Abstract：Objective To investigate the expression of mitochondrial ATP-sensitive potassium channels(mitoKATP)and mitochondrial functional alterations in the hearts of mice with heart failure related to diabetic cardiomyopathy(DCM).Methods Eighty male mice were randomly divided into control group,DCM group,DCM related diastolic heart failure group(DHF),and DCM related systolic heart failure group(SHF),with 20 mice in each group.The mice from the DCM group,DHF group,and SHF group were separately modeled correspondingly.Western blotting was used to detect the expression levels of mitoKATP subunits,electron microscopy was employed to observe the changes in mitochondrial ultrastructure,and Seahorse XFe96 analyzer was utilized to assess mitochondrial function in each group.Results Compared to the control group,the protein level of Kir6.1 subunit(which composes mitoKATP),basal respiratory capacity,ATP production capacity,maximal respiratory capacity,and respiratory reserve capacity of mitochondrial function in cardiomyocytes were significantly declined in the DCM,DHF,and SHF groups(P＜0.05).Transmission electron microscopy revealed swollen,rounded mitochondria with reduced matrix density,shortened and sparse cristae,and partial mitochondrial fusion in the DCM,DHF,and SHF groups.The mitochondrial basal respiratory capacity,ATP production capacity,and maximal respiratory capacity in cardiomyocytes from the DHF and SHF groups were significantly lower than those in the DCM group(P＜0.05).The SHF group had obviously lower mitochondrial basal respiratory capacity[44.0±1.5 pmol/(min·μg)vs 50.0±1.9 pmol/(min·μg),P＜0.05],ATP production capacity[31.0±2.0 pmol/(min·μg)vs 37.0±3.1 pmol/(min·μg),P＜0.05],and maximal respiratory capacity[59.0±4.0 pmol/(min·μg)vs 66.0±3.0 pmol/(min·μg),P＜0.05]when compared with the DHF group.Conclusion During the progression of DCM related heart failure,the expression levels of mitoKATP in mouse heart are continuously declined,while mitochondrial dysfunction in ventricular myocytes is progressively worsen.
Keywords：diabetic cardiomyopathiesheart failuremitochondriamitochondrial ATP-sensitive potassium channels
Publication Date：2025-12-15
Online Publishing Date：2025-12-29(First online date of this platform, not the publication date of the document)
Pages：4( 1727-1730 )