Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion

1 Neuromuscular Function Laboratory, Department of Occupational Therapy, Temple University, Philadelphia, Pennsylvania 19140; 2 United States Army Research Institute of Environmental Medicine, Natick 01760; 3 Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston 02115; and 4 Boston University, Sargent College of Health and Rehabilitation Sciences, Boston, Massachusetts 02215 Submitted 23 September 2003 ; accepted in final form 3 February 2004 ABSTRACT Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using 31 P-magnetic resonance spectroscopy in 16 men and women (36.9 ± 4.6 yr). The initial PCr resynthesis rate and time constant (T c ) were used as indicators of mitochondrial respiration after brief (10–12 s) and exhaustive (1–4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr ( r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP ( r = 0.77, P < 0.001), and no relationship with end-exercise pH ( r = -0.14, P = 0.34). The PCr T c was not as strongly related to PCr, Cr, PCr/Cr, and ADP ( r < 0.77, P < 0.001–0.18) and was significantly influenced by end-exercise pH ( r = -0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr T c . skeletal muscle; creatine kinase; mitochondria; phosphocreatine; phosphorous-31 magnetic resonance spectroscopy Address for reprint requests and other correspondence: S. A. Smith, Temple Univ., Neuromuscular Function Laboratory, Dept. of Occupational Therapy, 3307 North Broad St., Philadelphia, PA 19140 (E-mail: sinclair.smith{at}temple.edu ).