ABSTRACT
The adult mammalian heart, an oxidative organ, is extremely sensitive to hypoxia. The responsibility of alterations of cytosolic concentrations of the products and substrates of the ATPases, ATP, ADP inorganic phosphate, and proton in hypoxic cardiac failure is still controversial. In isolated organelles these metabolites have direct effects both on myofibrillar contractility and on mitochondrial respiration. In the isolated perfused heart, experimental models which affect the cytosolic concentration of a single metabolite are useful in understanding the influence of these metabolites on modulation of contractility in normoxia or hypoxia. Such models, including normoxic depletion of high energy phosphate contents or modification of the fluxes of creatine kinase, show that in a large range of concentration, heart function is merely dependent on the flux of energy production and transport rather than on the cytosolic concentrations of high energy phosphates, ATP, and phosphocreatine. The specificity of heart cell, the continuous coordination of the rates of energy production, utilization, and cytosolic transport are discussed in terms of intracellular compartmentation of creatine kinase isozymes. This compartmentation, characteristic of the adult mammalian cell, takes place during perinatal maturation together with the shift from a glycolytic to an oxidative type of metabolism and an increased susceptibility to hypoxia. The various roles of creatine kinase in energy buffering and transport is shown in relation to tissue specificity and pathophysiology.
