Intracellular high-energy phosphate transfer in normal and hypertrophied myocardium

The understanding of the physiologic role of the creatine kinase reaction has evolved in parallel with investigative technology. Since the creatine kinase reaction replenishes hydrolyzed ATP so rapidly, early studies detected only creatine phosphate hydrolysis during muscular contraction. Direct observation of ATP hydrolysis required creatine kinase inhibition and suggested that creatine phosphate provided an energy reserve. Elegant studies with isolated heart mitochondria provided evidence that the creatine kinase reaction regulates the rate of oxidative phosphorylation. The 31P nuclear magnetic resonance technique of magnetization transfer permitted the direct investigation of the creatine kinase reaction in intact organs and confirmed the classic observation that chemical flux through the creatine kinase reaction is coupled to mitochondrial energy production. Hearts from 18-month-old spontaneously hypertensive rats have as much as a 50% decrease in mitochondrial creatine kinase activity. Preliminary magnetization transfer studies in such a heart show a depressed relation between creatine kinase flux and cardiac performance. The results suggest that creatine kinase flux, as measured by magnetization transfer, is determined in part by creatine kinase isozyme composition and that these biochemical changes are associated with long-standing cardiac hypertrophy.