Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 283, Issue 2, Pages H598-H605Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00198.2002
Keywords
ischemia-reperfusion; reactive oxygen species; myocardium
Funding
- NHLBI NIH HHS [R01 HL 60164, R01 HL 63318] Funding Source: Medline
Ask authors/readers for more resources
Generation of reactive oxygen species (ROS) and intracellular Ca2+ overload are key mechanisms involved in ischemia-reperfusion (I/R)-induced myocardial injury. The relationship between I/R injury and Ca2+ overload has not been fully characterized. The increase in Na+/H+ exchanger (NHE-1) activity observed during I/R injury is an attractive candidate to link increased ROS production with Ca2+ overload. We have shown that low doses of H2O2 increase NHE-1 activity in an extracellular signal-regulated kinase (ERK)-dependent manner. In this study, we examined the effect of low doses of H2O2 on intracellular Ca2+ in fura 2-loaded, spontaneously contracting neonatal rat ventricular myocytes. H2O2 induced a time- and concentration-dependent increase in diastolic intracellular Ca2+ concentration that was blocked by inhibition of ERK1/2 activation with 5 muM U-0126 (88%) or inhibition of NHE-1 with 5 muM HOE-642 (50%). Increased NHE activity was associated with phosphorylation of the NHE-1 carboxyl tail that was blocked by U-0126. These results suggest that H2O2 induced Ca2+ overload is partially mediated by NHE-1 activation secondary to phosphorylation of NHE-1 by the ERK1/2 MAP kinase pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available