Intracellular energy transport and control of cardiac contraction.

Abstract

The participation of the intracellular creatine kinase system in energy transport in cardiac cells was studied further. The functional behavior of different but kinetically indistinguishable isoenzymes of creatine kinase (CK) in muscle cells is determined by their intracellular localization as is shown in this report for mitochondrial and sarcolemmal creatine kinases. The kinetics of the forward mitochondrial creatine kinase reaction is influenced by oxidative phosphorylation which increases the apparent affinity for ATP but does not change the kinetics of the reverse creatine kinase reaction. The molar content of creatine kinase in heart mitochondria was determined and found to be close to the content of adenine nucleotide translocase, thus supporting the concept of the tight functional relationship between those two mitochondrial proteins as a basis for effective phosphocreatine (PCr) production in mitochondria. In the sarcolemmal preparation, the antiport of Na+ and K+ is much more effectively supported by the sarcolemmal creatine kinase reaction than by an externally added ATP-regenerating system consisting of phosphoenolpyruvate and pyruvate kinase. The results of these experiments are taken to show the ability of sarcolemmal creatine kinase to maintain a very high phosphorylation potential in the vicinity of the active centers of the Na+ -K+ ATPase necessary to support the active transport of Na+ and K+ across the plasma membrane and to avoid a reversal of the ion gradient. Finally, it is concluded in this chapter that a rapid decrease in PCr content in the cells under anoxic or ischemic conditions may be one of the important factors in the impairment of cardiac contractile function under those conditions.