title: Analysis of the mechanisms of mitochondrial NADH regulation in cardiac trabeculae.
abstract: We have previously shown that increased cardiac work initially caused a rapid Ca(2+)-independent fall of mitochondrial [NADH] ([NADH](m)) to a minimum level, and this was followed by a slow Ca(2+)-dependent recovery toward control level (Brandes and Bers, Biophys. J. 71:1024-1035, 1996; Brandes and Bers, Circ. Res. 80:82-87, 1997). The purpose of this study is to improve our understanding of the factors that control [NADH](m) during increased work. [NADH](m) was monitored using fluorescence spectroscopy in intact rat trabeculae isolated from the right ventricular wall. Work was increased by increasing sarcomere length, pacing frequency, external [Ca(2+)], or by decreased temperature. The results were: 1) The initial fall of [NADH](m) during increased pacing frequency depends independently on increased myofilament work and on increased Ca(2+)-transport ATPase activity. 2) The [NADH](m) recovery process depends on average cytosolic [Ca(2+)] (Av[Ca(2+)](c)), but not on absolute work level. 3) The initial fall of [NADH](m) and the [NADH](m) recovery are similar whether increased work is associated with low frequency and high Ca(2+)-transient amplitude or vice versa (at the same myofilament work level and Av[Ca(2+)](c)). 4) The mechanisms associated with the smaller fall and recovery of [NADH](m) at 37 degrees C versus 27 degrees C, may be explained by lowered Av[Ca(2+)](c) and myofilament work. The NADH control mechanisms that operate at lower temperature are thus qualitatively similar at more physiological temperatures.
authors.affiliation: Department of Physiology, Loyola University, Chicago School of Medicine, 2160 South First Avenue, Maywood, Illinois 60153 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: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D002138:Calibration; D006321:Heart / Q000502:physiology*; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D008955:Models, Cardiovascular; D008956:Models, Chemical; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D051381:Rats; D012518:Sarcomeres / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
chemical_list: D009243:NAD; D000255:Adenosine Triphosphate; D002118:Calcium