Simultaneous measurements of mitochondrial NADH and Ca2+ during increased work in intact rat heart trabeculae

Rolf Brandes, Donald M Bers

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The main goal of this study is to investigate the role of mitochondrial [Ca2+], [Ca2+]m, in the possible up-regulation of the NADH production rate during increased workload. Such up-regulation is necessary to support increased flux through the electron transport chain and increased ATP synthesis rates. Intact cardiac trabeculae were loaded with Rhod-2(AM), and [Ca2+]m and mitochondrial [NADH] ([NADH]m) were simultaneously measured during increased pacing frequency. It was found that 53% of Rhod-2 was localized in mitochondria. Increased pacing frequency caused a fast, followed by a slow rise of the Rhod-2 signal, which could be attributed to an abrupt increase in resting cytosolic [Ca2+], and a more gradual rise of [Ca2+]m, respectively. When the pacing frequency was increased from 0.25 to 2 Hz, the slow Rhod-2 component and the NADH signal increased by 18 and 11%, respectively. Based on a new calibration method, the 18% increase of the Rhod-2 signal was calculated to correspond to a 43% increase of [Ca2+]m. There was also a close temporal relationship between the rise (time constant ∼25 s) and fall (time constant ∼65 s) of [Ca2+]m and [NADH]m when the pacing frequency was increased and decreased, respectively, suggesting that increased workload and [Ca2+]c cause increased [Ca2+]m and consequently up-regulation of the NADH production rate.

Original languageEnglish (US)
Pages (from-to)587-604
Number of pages18
JournalBiophysical Journal
Volume83
Issue number2
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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