Changes in potential controllers of human skeletal muscle respiration during incremental calf exercise

Abstract

The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60-100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS)

High-energy phosphate metabolism during two bouts of progressive calf exercise in humans measured by phosphorus-31 magnetic resonance spectroscopy

“…The work rate is given between the vertical lines. Statistically significant effects were marked with * (P <0.001) 31 P-MRS studies reported intramuscular mean pH values between 7.0 and 7.1 (Barstow et al 1994a(Barstow et al , 1994bFrancescato et al 2003;Marsh et al 1991;Rossiter et al 2001Rossiter et al , 2002. Collectively, the intramuscular pH of our volunteers at rest ranged between 6.94 and 7.02.…”

“…However, the prediction of the PCr kinetics, when employing the time constants derived from the moderate exercise to the heavy exercise, resulted in an underestimation of PCr hydrolysis, indicating a non-linear metabolism during heavy exercises. Other previous studies have reported an acceleration of PCr hydrolysis during work rates above the lactate threshold (Barstow et al 1994b;Marsh et al 1991). The lactate threshold occurs in a range between 60 to 80% of the peak work rate, as determined by spectroscopic measurement during exhaustive progressive muscle exercises in several previous studies (Barstow et al 1994b;Marsh et al 1991;McCreary et al 1996;Schocke et al 2004a).…”

“…Several previous 31 P-MRS investigations have shown that the linearity between PCr hydrolysis and workload is impaired when the pH in the muscle tissue falls below this so-called intracellular threshold, resulting in an acceleration of PCr hydrolysis via a pH-dependent impairment of creatine kinase activity (Barstow et al 1994b;Marsh et al 1991). A recently published study from our group, however, detected a significant decrease in pH during incremental exhaustive isotonic calf exercise that was not associated with an increase in PCr hydrolysis (Schocke et al 2004a).…”

“…Progressive or ramp muscle exercises are characterised by decreases in pH with a significant descent at peak work rates ranging between 60 and 80% (Barstow et al 1994b;Chwalbinska-Moneta et al 1989;Knuttgen and Saltin 1972;Marsh et al 1991). Several previous 31 P-MRS investigations have shown that the linearity between PCr hydrolysis and workload is impaired when the pH in the muscle tissue falls below this so-called intracellular threshold, resulting in an acceleration of PCr hydrolysis via a pH-dependent impairment of creatine kinase activity (Barstow et al 1994b;Marsh et al 1991).…”

Reply to “Letter to the editor: ‘Physiological implications of linear kinetics of mitochondrial respiration in vitro’”

“…Kemp's presentation provides a clear and important reminder that, in vivo, pH is not constant during the transition from a low to a higher metabolic rate, because phosphocreatine (PCr) splitting is a net alkalinizing reaction, which is balanced or exceeded by acidifying reactions (1). Moreover, the in vivo temporal discrepancies in these acid/base responses can allow distinction among models of control of respiration that otherwise appear inseparable (1).…”