Key result
In a rat model of cardiac hypertrophy, TREK-1 protein expression was upregulated by 89.8% in the endocardium, and the proportion of TREK-1 channel current in cardiac outward currents was enhanced.
TREK-1 protein expression and channel current are specifically increased in the endocardium during cardiac hypertrophy in rats, suggesting it may balance potassium ion flow and serve as a potential therapeutic target.
TREK-1 remodeling in hypertrophy may guide channel-targeted studies; leaves open therapeutic relevance in human disease.
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.
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Wang et al. (2012) studied Cardiac hypertrophy. Isoproterenol-induced cardiac hypertrophy vs. Normal control rats/cardiomyocytes was evaluated on TREK-1 protein expression and channel current. In a rat model of cardiac hypertrophy, TREK-1 protein expression was upregulated by 89.8% in the endocardium, and the proportion of TREK-1 channel current in cardiac outward currents was enhanced.
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