A THEORETICAL-MODEL OF SOME SPATIAL AND TEMPORAL ASPECTS OF THE MITOCHONDRION CREATINE-KINASE MYOFIBRIL SYSTEM IN MUSCLE

We describe a model of mitochondrial regulation in vivo which takes ac count of spatial diffusion of high-energy (ATP and phosphocreatine) an d low-energy metabolites (ADP and creatine), their interconversion by creatine kinase (which is not assumed to be at equilibrium), and possi ble functional 'coupling' between the components of creatine kinase as sociated with the mitochondrial adenine nucleotide translocase and the myofibrillar ATPase. At high creatine kinase activity, the degree of functional coupling at either the mitochondrial or ATPase end has litt le effect on relationships between oxidative ATP synthesis rate and sp atially-averaged metabolite concentrations. However, lowering the crea tine kinase activity raises the mean steady state ADP and creatine con centrations, to a degree which depends on the degree of coupling. At h igh creatine kinase activity, the fraction of flow carried by ATP is s mall. Lowering the creatine kinase activity raises this fraction, espe cially when there is little functional coupling. All metabolites show small spatial gradients, more so at low cytosolic creatine kinase acti vity, and unless there is near-complete coupling, so does net creatine kinase flux. During workjump transitions, spatial-average responses e xhibit near-exponential kinetics as expected, while concentration chan ges start at the ATPase end and propagate towards the mitochondrion, d amped in time and space.