Heart design: free ADP scales with absolute mitochondrial and myofibrillar volumes from mouse to human.
Our aim was to estimate a number of bioenergetic parameters in the beating mouse, rat and guinea pig heart in situ and compare the values to those in hearts of mammals over a 2000-fold range in body mass. For the mouse, rat and guinea pig heart, we report a phosphorylation ratio of 1005+/-50 (n=16), 460+/-32 (n=10) and 330+/-22 (n=5) mM(-1) and a free cytosolic [ADP] concentration of 13, 18 and 22 microM, respectively. When each parameter was plotted against body mass, they scaled closely to the quarter power (-0.28, r=0.99 and -0.23, r=0.97). A similar regression slope was found when the inverse of free [ADP] was plotted against absolute mitochondrial (slope=-0.26, r=0.99) and myofibrillar volumes (slope=-0.24, r=0.99). The similar slopes indicate that the ratio of absolute mitochondria and myofibrillar volumes in the healthy mammalian heart is a constant, and independent of body size. In conclusion, our study supports the hypothesis that the mammalian heart has a number of highly conserved thermodynamic and kinetic parameters that obey quarter-power laws linking the phosphorylation ratio, ATP turnover rates, free [ADP] and absolute mitochondrial volumes to body size. The results are discussed in terms of possible mechanisms and potential deviations from these laws in some disease states.
Dobson
Geoffrey P
GP
Department of Physiology and Pharmacology, James Cook University, 4811, Townsville, Qld, Australia. geoffrey.dobson@jcu.edu.au
Himmelreich
Uwe
U
D000244:Adenosine Diphosphate / Q000032:analysis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002302:Cardiac Output; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D006168:Guinea Pigs; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats; D012044:Regression Analysis
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate