title: An increased TREK-1-like potassium current in ventricular myocytes during rat cardiac hypertrophy.
abstract: To elucidate the expression and identify the functional changes of 2 pore domain potassium channel TREK-1 during cardiac hypertrophy in rats, left ventricular hypertrophy was induced by subcutaneous injection with isoproterenol. Western blot was used to detect the expression of TREK-1 channel protein, and inside-out and whole-cell recordings were used to record TREK-1 currents. The results showed that TREK-1 protein expression in endocardium was slightly higher than that in epicardium in control left ventricles. However, it was obviously upregulated by 89.8% during hypertrophy, 2.3-fold higher than in epicardium. Mechanical stretch, intracellular acidification, and arachidonic acid could activate a TREK-1-like current in cardiomyocytes. The slope conductances of cardiac TREK-1 and CHO/TREK-1 channels were 123 ± 7 and 113 ± 17 pS, respectively. The TREK-1 inhibitor L-3-n-butylphthalide (10 μM) reduced the currents in CHO/TREK-1 cells, normal cardiomyocytes, and hypertrophic cardiomyocytes by 48.5%, 54.3%, and 55.5%, respectively. The percentage of L-3-n-butylphthalide-inhibited outward whole-cell current in hypertrophic cardiomyocytes (23.7%) was larger than that in normal cardiomyocytes (14.2%). The percentage of chloroform-activated outward whole-cell current in hypertrophic cardiomyocytes (58.3%) was also larger than normal control (40.2%). Our results demonstrated that in hypertrophic rats, TREK-1 protein expression in endocardium was specifically increased and the ratio of TREK-1 channel current in cardiac outward currents was also enhanced. TREK-1 might balance potassium ion flow during hypertrophy and might be a potential drug target for heart protection.
authors.affiliation: 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.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.forename: Nan
authors.initials: N
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001572:Benzofurans; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C027125:3-n-butylphthalide; D007545:Isoproterenol