| First Author | Kamatham S | Year | 2019 |
| Journal | Pflugers Arch | Volume | 471 |
| Issue | 10 | Pages | 1263-1272 |
| PubMed ID | 31511966 | Mgi Jnum | J:293651 |
| Mgi Id | MGI:6453151 | Doi | 10.1007/s00424-019-02306-y |
| Citation | Kamatham S, et al. (2019) TREK-1 protects the heart against ischemia-reperfusion-induced injury and from adverse remodeling after myocardial infarction. Pflugers Arch 471(10):1263-1272 |
| abstractText | 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 Ca(2+) 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 Ca(2+) homeostasis. These data suggest that TREK-1 activation could be an effective strategy to provide cardioprotection against ischemia-induced damage. |
