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 M, 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 (C) 2002 Elsevier Science B.V. All rights reserved. states.