TREK-1 protects the heart against ischemia-reperfusion-induced injury and from adverse remodeling after myocardial infarction

Samuel Kamatham, Christopher M. Waters, Andreas Schwingshackl, Salvatore Mancarella

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)1263-1272
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Issue number10
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.


  • Ischemia-reperfusion
  • Mice
  • Myocardial infarction
  • Potassium channel
  • TREK-1
  • Telemetry

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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