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 Citations (Scopus)

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

Fingerprint

NAD
Myocardium
Respiratory Rate
Cell Respiration
Sarcomeres
Fluorescence Spectrometry
Oxidoreductases

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle. / Brandes, Rolf; Bers, Donald M.

In: Circulation Research, Vol. 80, No. 1, 1997, p. 82-87.

Research output: Contribution to journalArticle

@article{e2505343ee5040128f8e125a17aae1e3,
title = "Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle",
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.",
keywords = "ATP hydrolysis, dehydrogenase, force, heart, oxidative phosphorylation",
author = "Rolf Brandes and Bers, {Donald M}",
year = "1997",
language = "English (US)",
volume = "80",
pages = "82--87",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle

AU - Brandes, Rolf

AU - Bers, Donald M

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

KW - ATP hydrolysis

KW - dehydrogenase

KW - force

KW - heart

KW - oxidative phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=0030614778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030614778&partnerID=8YFLogxK

M3 - Article

VL - 80

SP - 82

EP - 87

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -