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+]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.
authors.affiliation: Department of Physiology, Loyola University Chicago, School of Medicine, Maywood, Ill., USA. rbrande@luc.edu
authors.forename: R
authors.initials: R
authors.lastname: Brandes
authors.forename: D M
authors.initials: DM
authors.lastname: Bers
mesh_terms: 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
chemical_list: D009243:NAD; D002118:Calcium