Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle

Rolf Brandes, Donald M Bers

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

It is not clear how mitochondrial energy production is regulated in intact tissue when energy consumption suddenly changes. Whereas mitochondrial [NADH] ([NADH](m)) may regulate cellular respiration rate and energetic state, it is not clear how [NADH](m) itself is controlled during increased work in vivo. We have varied work and [Ca2+] in intact cardiac muscle while assessing [NADH](m) using fluorescence spectroscopy. When increased work was accompanied by increasing average [Ca2+](c) (by increasing [Ca2+](o) or pacing frequency). [NADH](m) initially fell and subsequently recovered to a new steady state level. Upon reduction of work. [NADH](m) overshot and then returned to control levels. In contrast, when work was increased without increasing average [Ca2+](i), (by increasing sarcomere length). [NADH](m) fell similarly, but no recovery or overshoot was observed. This Ca2+- dependent recovery and overshoot may be attributed to Ca2+-dependent stimulation of mitochondrial dehydrogenases. We conclude that the immediate initial increase in respiration rate upon elevation of work is not activated by increased [NADH](m) (since [NADH](m) rapidly fell) or by [Ca2+](c), (since work could also be increased at constant [Ca2+](c)). However, during sustained high work, a Ca2+-dependent mechanism causes slow recovery of [NADH](m) toward control values. This demonstrates a Ca2+-dependent feed- forward control mechanism of cellular energetics in cardiac muscle during increased work.

Original languageEnglish (US)
Pages (from-to)82-87
Number of pages6
JournalCirculation Research
Volume80
Issue number1
StatePublished - 1997
Externally publishedYes

Keywords

  • ATP hydrolysis
  • dehydrogenase
  • force
  • heart
  • oxidative phosphorylation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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