Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes.

ABSTRACT:

Background

Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na(+) ([Na(+)](i)) reduces mitochondrial Ca(2+) ([Ca(2+)](m)) by accelerating Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca(2+)](m), we speculated that in failing myocytes, elevated [Na(+)](i) promotes oxidative stress.

Methods and results

We used a patch-clamp-based approach to simultaneously monitor cytosolic and mitochondrial Ca(2+) and, alternatively, mitoch

SUBMITTER: Kohlhaas M 

PROVIDER: S-EPMC2946079 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature