Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle.
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+]c 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+]o (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 [Ca2+]o (since work could also be increased at constant [Ca2+]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.
Brandes
R
R
Department of Physiology, Loyola University Chicago, School of Medicine, Maywood, Ill., USA. rbrande@luc.edu
Bers
D M
DM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004734:Energy Metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D009243:NAD; D002118:Calcium