Increased work in cardiac trabeculae causes decreased mitochondrial NADH fluorescence followed by slow recovery

Rolf Brandes, Donald M Bers

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The oxidative phosphorylation rate in isolated mitochondria is stimulated by increased [ADP], resulting in decreased [NADH]. In intact hearts, however, increased mechanical work has generally not been shown to cause an increase in [ADP]. Therefore, increased [NADH] has been suggested as an alternative for stimulating the phosphorylation rate. Such a rise in [NADH] could result from stimulation of various substrate dehydrogenases by increased intracellular [Ca2+] (e.g., during increased pacing frequency). We have monitored mitochondrial [NADH] in isolated rat ventricular trabeculae, using a novel fluorescence spectroscopy method where a native fluorescence signal was used to correct for motion artifacts. Work was controlled by increased pacing frequency and assessed using time-averaged force. At low-pacing rates (~0.1 Hz), [NADH] immediately decreased during contraction and then slowly recovered (~5 s) before the next contraction. At higher rates, [NADH] initially decreased by an amount related to pacing rate (i.e., work). However, during prolonged stimulation, [NADH] slowly (~60 s) recovered to a new steady-state level below the initial level. We conclude that 1) during increased work, oxidative phosphorylation is not initially stimulated by increased mitochondrial [NADH]; and 2) increased pacing frequency slowly causes stimulation of NADH production.

Original languageEnglish (US)
Pages (from-to)1024-1035
Number of pages12
JournalBiophysical Journal
Volume71
Issue number2
StatePublished - Aug 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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