Institutional members access full text with Ovid®

Functional Study of TREK-1 Potassium Channels During Rat Heart Development and Cardiac Ischemia Using RNAi Techniques

Yang, Xiaojuan PhD*,†; Guo, Peng PhD*; Li, Jiang MS*; Wang, Weiping PhD*; Xu, Shaofeng BS*; Wang, Ling BS*; Wang, Xiaoliang MD*

Journal of Cardiovascular Pharmacology: August 2014 - Volume 64 - Issue 2 - p 142–150
doi: 10.1097/FJC.0000000000000099
Original Article

Abstract: 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.

*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: wangxl@imm.ac.cn).

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.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org).

Received October 23, 2013

Accepted March 16, 2014

© 2014 by Lippincott Williams & Wilkins.