Affiliation:
1. the Department of Physiology, Loyola University Chicago, School of Medicine, Maywood, Ill. E-mail rbrande@luc.edu
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 [Ca
2+
] in intact cardiac muscle while assessing [NADH]
m
using fluorescence spectroscopy. When increased work was accompanied by increasing average [Ca
2+
]
c
(by increasing [Ca
2+
]
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 [Ca
2+
]
c
(by increasing sarcomere length), [NADH]
m
fell similarly, but no recovery or overshoot was observed. This Ca
2+
-dependent recovery and overshoot may be attributed to Ca
2+
-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 [Ca
2+
]
c
(since work could also be increased at constant [Ca
2+
]
c
). However, during sustained high work, a Ca
2+
-dependent mechanism causes slow recovery of [NADH]
m
toward control values. This demonstrates a Ca
2+
-dependent feed-forward control mechanism of cellular energetics in cardiac muscle during increased work.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
113 articles.
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