Mitochondrial creatine kinase in mammalian myocardial cells in culture.

Previous studies on the energy metabolism of rat myocardial cells in culture supported the hypothesis that the creatine-phosphorylcreatine-creatine kinase system is essential for intracellular transport of energy from the mitochondria to the myofibrils and in the regulation of energy production to meet energy utilization. Effective functional compartmentation of ATP could result from the binding of creatine kinase to cellular organelles (e.g., myofibrils and mitochondria) so that the high-energy charge at the myofibrils is maintained by the reverse creatine kinase reaction, whereas phosphorylcreatine is synthesized mainly at the mitochondria in the forward creatine kinase reaction. It was essential to demonstrate the presence of mitochondrial creatine kinase to support the hypothesis. Using polyacrylamide gel electrophoresis and electrophoresis on cellulose acetate strips, the mitochondrial creatine kinase isozyme, as well as MM, MB, and BB isozymes, has now been demonstrated in myocardial cells in culture. Nonmuscle cells in culture also derived from neonatal rat hearts lack the mitochondrial creatine kinase isozyme. Total creatine kinase in myocardial cells is greatly decreased by treatment of the cells with adriamycin, a cardiotoxic chemotherapeutic agent, and the relative amounts of the isozymes are altered. The mitochondrial creatine kinase seems to be reduced less than either the BB or MM isozymes.