Creatine kinase deficiency in striated mouse muscle : biochemical and physiological studies

The balance between ATP energy demand and supply is essential in muscle cells. The creatine kinase system fulfils both a transporting and buffering role in muscle cells, whereby fluctuations in ATP free-energy demand can be counterbalanced. Removal of the creatine kinase proteins with the aid of genetic engineering is explored in this thesis manuscript. Although creatine kinase ablation is non-lethal, distinct changes are known to occur in the muscle free-energy balance. Especially during intensive muscle exercise the lack of creatine kinase is apparent through decreased mechanical performance. Our studies on isolated mitochondria indicate to increased mitochondrial capacity in fast- twitch muscles and a shift in the operational domain of mitochondrial activity. These results were further confirmed using isolated hindleg muscles. Oxygen consumption at rest was found to be increased. In addition, the activation and deactivation of mitochondrial respiration upon muscle stimulation was found to be quicker in mouse muscles lacking creatine kinase. This shows that the exclusive transport function of CK between the sites of energy demand (myosin) and supply (mitochondria) is not a prerequisite for intracellular communication, which argues against the so-called "shuttle" concept in its extreme form