Abstract
The mitochondrial NADH fluorescence firstly decreased and then increased when the positive staircase of contraction was induced by increasing the stimulation rate in guinea-pig ventricular cells. We studied mechanisms by incorporating the well-established model of oxidative phosphorylation (Korzeniewski & Zoladz, 2001) in our membrane excitation-contraction Kyoto model. When the stimulation rate was switched to 3.3 Hz after establishing a steady-state at 0.1 Hz, the mitochondrial NADH concentration declined and reached a new steady state, and cytoplasmic ATP concentration significantly decreased. Assuming a delayed activation of NADH production during 3.3 Hz stimulation well reconstructed the biphasic response of mitochondrial NADH and remarkably attenuated the decrease in cytoplasmic ATP. Thus, the model supported our hypothesis that the initial decrease in mitochondrial NADH is due to feedback control by ADP (Chance and Williams, 1956), while the delayed increase in mitochondrial NADH is caused by the activation of NADH production. The model predicted that this activation of NADH production attenuates the contribution of feedback control by about 25% when compared at the same rate of ATP synthesis during 3.3 Hz stimulation. [Jpn J Physiol 55 Suppl:S93 (2005)]
