TREK-1 protects the heart against ischemia-reperfusion-induced injury and from adverse remodeling after myocardial infarction
The TWIK-related K+ channel (TREK-1) is a two-pore-domain potassium channel that produces background leaky potassium currents. TREK-1 has a protective role against ischemia-induced neuronal damage. TREK-1 is also expressed in the heart, but its role in myocardial ischemia-reperfusion (IR)-induced injury has not been examined. In the current study, we used a TREK-1 knockout (KO) mouse model to show that TREK-1 has a critical role in the cardiac I/R-induced injury and during remodeling after myocardial infarction (MI). At baseline, TREK-1 KO mice had similar blood pressure and heart rate as the wild-type (WT) mice. However, the lack of TREK-1 was associated with increased susceptibility to ischemic injury and compromised functional recovery following ex vivo I/R-induced injury. TREK-1 deficiency increased infarct size following permanent coronary artery ligation, resulting in greater systolic dysfunction than the WT counterpart. Electrocardiographic (ECG) analysis revealed QT interval prolongation in TREK-1 KO mice, but normal heart rate (HR). Acutely isolated TREK-1 KO cardiomyocytes exhibited prolonged Ca2+ transient duration associated with action potential duration (APD) prolongation. Our data suggest that TREK-1 has a protective effect against I/R-induced injury and influences the post-MI remodeling processes by regulating membrane potential and maintaining intracellular Ca2+ homeostasis. These data suggest that TREK-1 activation could be an effective strategy to provide cardioprotection against ischemia-induced damage.
KeywordsPotassium channel Ischemia-reperfusion Mice Telemetry Myocardial infarction TREK-1
We would like to thank Mr. Jesse Gammons for his comments during the editing of this manuscript.
SM was the principal investigator of the study and participated in the design of the study, carried out the experiments, performed the statistical analysis, and drafted the manuscript. SK analyzed Ca2+ transients measurements. AS and CW provided the TREK-1 KO mice and edited the manuscript. All authors read and approved the final manuscript.
This work was supported by intramural department funds and by National Heart, Lung and Blood Institute (grant number HL114869, to Dr. S.M. and HL131526 and HL123540 to CMW).
Compliance with ethical standards
All animal experiments were performed according to protocols approved by the Institutional Animal Care and Use Committees and comply with USA regulations on animal experimentation.
Conflict of interest
The authors declare that they have no competing interests.
Informed consent was obtained from all individual participants included in the study.
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