To explore the physiological and pathological significance of the 2-pore domain potassium channel TWIK-related K+ (TREK)-1 in rat heart, its expression and role during heart development and cardiac ischemia were investigated. In the former study, the ventricles of Sprague Dawley rats were collected from embryo day 19 to postnatal 18 months and examined for mRNA and protein expression of TREK-1. It was found that both increased during development, reached a maximum at postnatal day 28, and remained higher at postnatal day 3 through to postnatal 18 months. In the latter study, protein expression of TREK-1 was examined after initiation of acute heart ischemia by ligation of the left anterior descending coronary artery. TREK-1 expression was found to be increased in the endocardium but unchanged in the epicardium. In primary cultured rat neonatal ventricular myocytes subjected to hypoxia (oxygen–glucose deprivation), TREK-1 expression was increased. In cultured neonatal cardiomyocytes, silencing of the TREK-1 gene by lentivirus delivery of the short-hairpin RNAs, L-sh-492 and L-sh-605, was found to promote their viability and number. In addition, both short-hairpin RNA provided protection against hypoxia-induced injury to cardiomyocytes in vitro. These results suggest that TREK-1 plays an important role in neonatal rat heart development and downregulation of TREK-1 may provide protection against ischemic injury. It seems that TREK-1 is a potential drug target for treatment of acute heart ischemia.
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*State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; and
†Department of Pharmacy, People's Hospital of Anyang City, Anyang, China.
Reprints: Xiaoliang Wang, MD, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan St, Beijing 100050, China (e-mail: email@example.com).
Supported by The National Natural Science Foundation of China (No 90913019) and National Major Special Project on New Drug Innovation of China (No 2012ZX09301002-004).
The authors report no conflicts of interest.
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Received October 23, 2013
Accepted March 16, 2014