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Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction

Authors :
Fu-Ming Shen
Xia Tao
Ji-Kuai Chen
Ya-Ping Deng
Guo-Jun Jiang
Min Ni
Ting Zhao
Zhong-Wei Yang
Source :
Cardiovascular Diabetology
Publisher :
Springer Nature

Abstract

Background Cardiac dysfunction is well-described in endotoxemia and diagnosed in up to 60% of patients with endotoxic shock. ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia. Methods Kir6.2 subunits knockout (Kir6.2−/−) and wild-type (WT) mice were injected with LPS to induce endotoxemia. Cardiac function was monitored by echocardiography. Left ventricles were taken for microscopy (both light and electron) and TUNEL examination. Serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, and tumor necrosis factor-α (TNF-α) levels in both serum and left ventricular tissues were determined. Results Compared to WT, Kir6.2−/− mice showed significantly declined cardiac function 360 min after LPS administration, aggravated myocardial damage and elevated serum LDH and CK activities. Apoptotic cells were obviously increased in heart tissues from Kir6.2−/− mice at 90, 180 and 360 min. TNF-α expression in both serum and heart tissues of Kir6.2−/− mice was significantly increased. Conclusions We conclude that Kir6.2 subunits are critical in resistance to endotoxemia-induced cardiac dysfunction through reducing myocardial damage by inhibition of apoptosis and inflammation. KATP channels blockers are extensively used in the treatment of diabetes, their potential role should therefore be considered in the clinic when patients treated with antidiabetic sulfonylureas are complicated by endotoxemia.

Details

Language :
English
ISSN :
14752840
Volume :
12
Issue :
1
Database :
OpenAIRE
Journal :
Cardiovascular Diabetology
Accession number :
edsair.doi.dedup.....be1f5931927623ee7eb7b55edddb4368
Full Text :
https://doi.org/10.1186/1475-2840-12-75