A linear model of muscle respiration explains monoexponential phosphocreatine changes

1988 ◽  
Vol 254 (4) ◽  
pp. C548-C553 ◽  
Author(s):  
R. A. Meyer
Keyword(s):  
Time Constant ◽  
Atp Hydrolysis ◽  
Resonance Spectroscopy ◽  
Analog Model ◽  
Electrical Analog ◽  
First Order ◽  
Total Creatine ◽  
Creatine Kinase Reaction ◽  
Gastrocnemius Muscles ◽  
Mean Time

Phosphocreatine (PCr) content was measured by phosphorus nuclear magnetic resonance spectroscopy in the gastrocnemius muscles of pentobarbital-anesthetized rats during and after twitch stimulation at rates up to 0.75 Hz. The monoexponential time constant for PCr changes was similar at the onset of vs. during recovery after stimulation and was not significantly different for different stimulation rates (mean time constant 1.44 min). Steady-state PCr level during stimulation was linearly related to the product of stimulation rate times peak twitch force. These results are shown to be consistent with a simple first-order electrical analog model of oxidative metabolism that is applicable at submaximal oxidative rates. The model assumes equilibrium of the creatine kinase reaction, which is modeled as a chemical capacitor, with capacitance proportional to the total creatine level, and PCr level proportional to the cytosolic free energy of ATP hydrolysis.

Linear relation between time constant of oxygen uptake kinetics, total creatine, and mitochondrial content in vitro

2008 ◽  
Vol 294 (1) ◽  
pp. C79-C87 ◽  
Author(s):  
Brian Glancy ◽  
Thomas Barstow ◽  
Wayne T. Willis
Keyword(s):  
Time Constant ◽  
Mitochondrial Protein ◽  
Oxygen Uptake Kinetics ◽  
Analog Model ◽  
Electrical Analog ◽  
Skeletal Muscle Mitochondria ◽  
Rate Of Oxygen Consumption ◽  
Total Creatine ◽  
Kinetics Of

Following the onset of moderate aerobic exercise, the rate of oxygen consumption (Jo) rises monoexponentially toward the new steady state with a time constant (τ) in the vicinity of 30 s. The mechanisms underlying this delay have been studied over several decades. Meyer's electrical analog model proposed the concept that the τ is given by τ = Rm· C, where Rm is mitochondrial resistance to energy transfer, and C is metabolic capacitance, determined primarily by the cellular total creatine pool (TCr = phosphocreatine + creatine). The purpose of this study was to evaluate in vitro the Jo kinetics of isolated rat skeletal muscle mitochondria at various levels of TCr and mitochondrial protein. Mitochondria were incubated in a medium containing 5.0 mM ATP, TCr pools of 0–1.5 mM, excess creatine kinase, and an ATP-splitting system of glucose + hexokinase (HK). Pyruvate and malate (1 mM each) were present as oxidative substrates. Jo was measured across time after HK was added to elicit one of two levels of Jo (40 and 60% of state 3). At TCr levels (in mM) of 0.1, 0.2, 0.3, 0.75, and 1.5, the corresponding τ values (s, means ± SE) were 22.2 ± 3.0, 36.3 ± 2.2, 65.7 ± 4.3, 168.1 ± 22.2, and 287.3 ± 25.9. Thus τ increased linearly with TCr ( R2 = 0.916). Furthermore, the experimentally observed τ varied linearly and inversely with the mitochondrial protein added. These in vitro results consistently conform to the predictions of Meyer's electrical analog model.

Linear dependence of muscle phosphocreatine kinetics on total creatine content

1989 ◽  
Vol 257 (6) ◽  
pp. C1149-C1157 ◽  
Author(s):  
R. A. Meyer
Keyword(s):  
Linear Models ◽  
Adenine Nucleotide ◽  
Respiratory Control ◽  
Staircase Effect ◽  
Total Creatine ◽  
Creatine Kinase Reaction ◽  
Gastrocnemius Muscles ◽  
The Relationship ◽  
Hydrolysis Of ◽  
Stimulation Of

Phosphorus nuclear magnetic resonance (NMR) spectra and twitch tension were recorded during stimulation of gastrocnemius muscles of pentobarbital sodium-anesthetized rats which had been fed the creatine analogue beta-guanidinopropionic acid (beta-GPA, 2% diet) for periods from 0 (control) to 8 wk. Total creatine content of unstimulated muscles decreased by 42, 67, 82, and 88% compared with controls after 2-, 4-, 6-, and 8-wk feeding, respectively. The staircase effect observed in control muscles during 8 min of twitch stimulation at 0.25, 0.5, and 0.75 Hz was reduced after 2- to 8-wk beta-GPA feeding. However, after 6- to 8-wk feeding, the twitch force at the end of 8 min of stimulation was not different from controls. The time constant for phosphocreatine (PCr) changes at the onset of and during recovery after stimulation was proportional to total creatine content. The relationship between PCr content and twitch rate times force at the end of stimulation was linear, with slope proportional to total creatine content. PCr content in beta-GPA-fed animals was transiently greater during recovery than before stimulation, suggesting a regulatory effect of the inorganic phosphate released by hydrolysis of phosphorylated beta-GPA. The results are consistent with linear models of respiratory control in which the creatine kinase reaction acts as a simple buffer of adenine nucleotide levels.

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

1994 ◽  
Vol 77 (5) ◽  
pp. 2169-2176 ◽  
Author(s):  
T. J. Barstow ◽  
S. D. Buchthal ◽  
S. Zanconato ◽  
D. M. Cooper
Keyword(s):  
Atp Hydrolysis ◽  
Plantar Flexion ◽  
Work Rate ◽  
Resonance Spectroscopy ◽  
Calf Exercise ◽  
Creatine Kinase Reaction ◽  
Human Calf ◽  
Menten Constant ◽  
Homogeneous Tissue ◽  
Plantar Flexion Exercise

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)

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Impaired oxygen delivery to muscle in chronic fatigue syndrome

1999 ◽  
Vol 97 (5) ◽  
pp. 603-608 ◽  
Author(s):  
Kevin K. MCCULLY ◽  
Benjamin H. NATELSON
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Time Constant ◽  
Oxidative Metabolism ◽  
Oxygen Delivery ◽  
Specific Effect ◽  
Chronic Fatigue ◽  
Medial Gastrocnemius ◽  
Resonance Spectroscopy ◽  
Activity Levels ◽  
Fatigue Syndrome

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced oxygen delivery to muscles. Patients with CFS according to CDC (Center for Disease Control) criteria (n = 20) were compared with normal sedentary subjects (n = 12). Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemia oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous-wavelength near-IR spectroscopy. Phosphocreatine resynthesis was measured simultaneously using 31P magnetic resonance spectroscopy. The time constant of oxygen delivery was significantly reduced in CFS patients after exercise (46.5±16 s; mean±S.D.) compared with that in controls (29.4±6.9 s). The time constant of oxygen delivery was also reduced (20.0±12 s) compared with controls (12.0±2.8 s) after cuff ischaemia. Oxidative metabolism was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative metabolism and recovery of oxygen delivery. In conclusion, oxygen delivery was reduced in CFS patients compared with that in sedentary controls. This result is consistent with previous studies showing abnormal autonomic control of blood flow. Reduced oxidative delivery in CFS patients could be specifically related to CFS, or could be a non-specific effect of reduced activity levels in these patients. While these results suggest that reduced oxygen delivery could result in reduced oxidative metabolism and muscle fatigue, further studies will be needed to address this issue.

Effects of the Anti-Migraine Drug Sumatriptan on Muscle Energy Metabolism: Relationship to Side-Effects

Cephalalgia ◽  
2000 ◽  
Vol 20 (1) ◽  
pp. 39-44 ◽  
Author(s):  
MD Boska ◽  
KMA Welch ◽  
L Schultz ◽  
J Nelson
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Side Effects ◽  
Kinetic Data ◽  
Oxygen Storage ◽  
Resonance Spectroscopy ◽  
Sumatriptan Succinate ◽  
Muscle Energy ◽  
Creatine Kinase Reaction ◽  
Muscle Energy Metabolism

Sumatriptan succinate (Imitrex) is a 5-HT(5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5–20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.

scholarly journals Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle

1999 ◽  
Vol 87 (5) ◽  
pp. 1768-1775 ◽  
Author(s):  
C. A. Combs ◽  
A. H. Aletras ◽  
R. S. Balaban
Keyword(s):  
Free Energy ◽  
Atp Hydrolysis ◽  
Tibialis Anterior Muscle ◽  
Respiratory Control ◽  
Oxidative Capacity ◽  
Resonance Spectroscopy ◽  
Muscle Action ◽  
Pooled Data ◽  
Muscle Actions

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867–874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo ( n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and 31P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 μM or decrease the free energy of ATP hydrolysis to −55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 μmol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions ( P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

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