Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis

Zhang,Xiaohui; Zhang,Xiaohua; Xiong,Yiqun; Xu,Chaoying; Liu,Xinliang; Lin,Jian; Mu,Guiping; Xu,Shaogang; Liu,Wenhe

doi:10.3892/ijmm.2016.2664

Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis

Authors:
- Xiaohui Zhang
- Xiaohua Zhang
- Yiqun Xiong
- Chaoying Xu
- Xinliang Liu
- Jian Lin
- Guiping Mu
- Shaogang Xu
- Wenhe Liu
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Affiliations: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China, Cardiac Signaling Center, Medical University of South Carolina, Charleston, SC 29425, USA
Published online on: July 5, 2016 https://doi.org/10.3892/ijmm.2016.2664
Pages: 758-766
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The sarcolemmal ATP-sensitive K+ (sarcKATP) channel plays a cardioprotective role during stress. However, the role of the sarcKATP channel in the apoptosis of cardiomyocytes and association with mitochondrial calcium remains unclear. For this purpose, we developed a model of LPS-induced sepsis in neonatal rat cardiomyocytes (NRCs). The TUNEL assay was performed in order to detect the apoptosis of cardiac myocytes and the MTT assay was performed to determine cellular viability. Exposure to LPS significantly decreased the viability of the NRCs as well as the expression of Bcl-2, whereas it enhanced the activity and expression of the apoptosis-related proteins caspase-3 and Bax, respectively. The sarcKATP channel blocker, HMR-1098, increased the apoptosis of NRCs, whereas the specific sarcKATP channel opener, P-1075, reduced the apoptosis of NRCs. The mitochondrial calcium uniporter inhibitor ruthenium red (RR) partially inhibited the pro-apoptotic effect of HMR-1098. In order to confirm the role of the sarcKATP channel, we constructed a recombinant adenovirus vector carrying the sarcKATP channel mutant subunit Kir6.2AAA to inhibit the channel activity. Kir6.2AAA adenovirus infection in NRCs significantly aggravated the apoptosis of myocytes induced by LPS. Elucidating the regulatory mechanisms of the sarcKATP channel in apoptosis may facilitate the development of novel therapeutic targets and strategies for the management of sepsis and cardiac dysfunction.

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