Myocardial death and dysfunction after ischemia-reperfusion injury require CaMKIIδ oxidation

Yuejin Wu, Qinchuan Wang, Ning Feng, Jonathan M. Granger, Mark E. Anderson

Research output: Contribution to journalArticlepeer-review


Reactive oxygen species (ROS) contribute to myocardial death during ischemia-reperfusion (I/R) injury, but detailed knowledge of molecular pathways connecting ROS to cardiac injury is lacking. Activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKIIδ) is implicated in myocardial death, and CaMKII can be activated by ROS (ox-CaMKII) through oxidation of regulatory domain methionines (Met281/282). We examined I/R injury in mice where CaMKIIδ was made resistant to ROS activation by knock-in replacement of regulatory domain methionines with valines (MMVV). We found reduced myocardial death, and improved left ventricular function 24 hours after I/R injury in MMVV in vivo and in vitro compared to WT controls. Loss of ATP sensitive K+ channel (KATP) current contributes to I/R injury, and CaMKII promotes sequestration of KATP from myocardial cell membranes. KATP current density was significantly reduced by H2O2 in WT ventricular myocytes, but not in MMVV, showing ox-CaMKII decreases KATP availability. Taken together, these findings support a view that ox-CaMKII and KATP are components of a signaling axis promoting I/R injury by ROS.

Original languageEnglish (US)
Article number9291
JournalScientific reports
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General


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