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(Circulation Research. 1997;80:82-87.)
© 1997 American Heart Association, Inc.

Articles

Intracellular Ca²⁺ Increases the Mitochondrial NADH Concentration During Elevated Work in Intact Cardiac Muscle

Rolf Brandes, Donald M. Bers

the Department of Physiology, Loyola University Chicago, School of Medicine, Maywood, Ill. E-mail rbrande@luc.edu

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⁺]_c (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.

Key Words: heart • force • ATP hydrolysis • oxidative phosphorylation • dehydrogenase

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