title: Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis.
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.
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cardiac Signaling Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Xu
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Mu
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Shaogang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Wenhe
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology; D054086:KATP Channels / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism*; D014162:Transfection; D014665:Vasodilator Agents / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D001549:Benzamides; D053148:Caspase 3; D006146:Guanidines; D054086:KATP Channels; D008070:Lipopolysaccharides; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D014665:Vasodilator Agents; D051028:bcl-2-Associated X Protein; D000099161:Kcnj11 Channel; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; C410297:HMR 1098