Abstract 345: Dramatic ATP Depletion Without Concomitant Declines in ATP Synthesis Rates Suggests Impaired Energy Metabolism Mechanisms in Adrenergic-Deficient Mouse Embryos
High cardiac energy demands increase during embryonic development, requiring oxidative phosphorylation converting ADP to ATP in mitochondria to meet these demands. We have recently shown that adrenergic hormones are required to maintain sufficient cardiac energy metabolism during embryonic development, but the specific mechanism(s) underlying this regulation are not known. Mouse embryos lacking adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to targeted loss of the essential dopamine β-hydroxylase (Dbh) gene, have remarkably decreased steady-state ATP/ADP ratios. To determine if ATP synthesis was affected, we examined the rate of ATP formation in adrenergic-deficient and control embryonic hearts. Our rate data have shown that despite > 50-fold decrease of steady-state ATP concentrations in Dbh-/- embryos, the rate of ATP synthesis was not significantly different in adrenergic-competent and deficient embryos. This indicates that respiratory complexes in mitochondria are capable of producing ATP in adrenergic-deficient embryos, and suggest that ATP is either consumed at a faster rate than it is produced or its production is limited in vivo due to limited access to metabolic substrates (“starvation”). These findings reveal new mechanistic insights about how adrenergic hormones regulate energy metabolism during embryonic development.
Author Disclosures: J.N.R. Peoples: None. C. Baker: None. S. Ebert: None.
- © 2015 by American Heart Association, Inc.