Effect of ischemia and denervation on metabolism of fast and slow mammalian skeletal muscle

doi:10.1016/0014-4886(70)90161-5

Experimental Neurology

Volume 28, Issue 1, July 1970, Pages 46-63

https://doi.org/10.1016/0014-4886(70)90161-5 Get rights and content

Abstract

Changes in major energy reserves, lactate and inorganic phosphate, were followed in innervated and denervated extensor digitorum longus and soleus muscles of the rat during ischemia. In the innervated muscles levels of energy reserves were higher in extensor than in soleus muscles. After denervation energy stores were significantly decreased in both types of muscle. During ischemia, the pattern of recruitment of energy reserves was similar in innervated and denervated muscles; however, ATP levels decreased most rapidly in extensor muscles denervated 5 days previously. Phosphocreatine decreased rapidly in all muscles during ischemia; glycogen, glucose, and ATP fell more slowly while glucose-6-P increased. From these changes, the initial rates of energy use during ischemia were calculated to be 12.4 and 11.2 mmoles/kg wet tissue per minute in innervated extensor and soleus muscles, respectively. Five days after denervation energy use rates decreased to 64 and 52% of control values in extensor and soleus muscles, respectively. Initial rates of lactate accumulation were slower in innervated than denervated muscles; however, glycogen and glucose were utilized at faster rates in innervated muscles. In view of these findings, it is concluded that reduction of metabolic rate is the chief factor involved in the decrease of high energy phosphate in both fast and slow denervated muscle.

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The effect of surgical and chemical denervation on ischaemia/reperfusion injury of skeletal muscle
2012, Journal of Plastic, Reconstructive and Aesthetic Surgery
Denervation decreases skeletal muscle’s energy needs and alters its metabolism and circulation. Our study was designed in two stages to investigate the effects of surgical and chemical denervation on the ischaemia/reperfusion injury of skeletal muscle. Degenerative histological analysis, apoptosis scoring and tissue levels of malonyl-di-aldehyde (MDA) and nitric oxide end products (NOx) were studied to understand the extent of ischaemia/reperfusion injury of skeletal muscles.
In the first stage, the effect of surgical denervation was investigated in four groups each containing six rats. The right biceps femoris muscle was used as the experimental muscle flap model. In the control group, only the ischaemia/reperfusion cycle was applied. Ischaemia was created by a tourniquet strictly wrapping the right lower extremity for 4 h. After ischaemia, the tourniquet was cut, and the extremity was reperfused for another 4 h. In the experimental groups, surgical denervation was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle.
On the second stage, the effect of chemical denervation with botulinum toxin type-A (BoNT-A) was investigated in three groups, each containing six rats. In the experimental groups, BoNT-A was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle.
The control group had the worst scores in all experiment parameters. Degenerative histology and apoptosis scores were significantly better in groups to which BoNT-A and SD were applied 1 or 7 days before the ischaemia/reperfusion cycle. Regarding tissue levels of MDA and NOx, the experiment groups had significantly better scores comparing to the control group.
Both surgical and chemical denervation applied before muscle transfer increased muscle ischaemia tolerance. With similar experimental outcomes, denervation with BoNT-A can be preferred to surgical denervation because of its abundant clinical availability and it can be applied without any secondary surgery.
Studies on the inhibition by chlorpromazine of myotonia induced by ion channel modulators in mouse skeletal muscle
1993, European Journal of Pharmacology
The myotonic activity of mouse soleus and extensor digitorum longus muscles induced by either a combination of K⁺ channel blockers (4-aminopyridine) and a Cl⁻ channel blocker (9-anthracene carboxylic acid) or a Cl⁻ channel blocker in low Ca²⁺ (0.25 mM) Krebs or a Na⁺ channel activator (veratridine) was characterized in this paper. Myotonic activity was characterized by an increase in both the contraction amplitude and contraction duration accompanied by stimulus-related repeated action potentials. The slow soleus and fast extensor digitorum longus muscles appeared to differ in their responses to these ion channel modifiers. Nevertheless, chlorpromazine at a low concentration of 1 μM significantly inhibited all kinds of myotonic activity; it reduced the prolonged contraction duration and attenuated the stimulus-related repeated action potential firing. This depressant action of chlorpromazine was apparently not correlated with inhibition of either calmodulin or phospholipase A₂ activity, since the myotonic depressant action of calmodulin inhibitors, such as dibucaine, flunarizine, chlorpromazine, trifluoperazine and diltiazem, was unrelated to their potency in inhibiting the activity of calmodulin or phospholipase A₂. However, phosphatidylcholine was found to inhibit the myotonic depressant action of chlorpromazine. It is therefore, tentatively concluded that chlorpromazine interacted with membrane phospholipids, thereby changing membrane ion channel activity and depressing myotonic activity. These findings indicate that chlorpromazine might be useful in the management of clinical myotonia.
The study of energy metabolism in denervated skeletal muscle with <sup>31</sup>P-NMR
1990, Comparative Biochemistry and Physiology -- Part A: Physiology
- 1.
  1. The denervated frog sartorius muscle showed a decrease in the energy store more than that in the control.
- 2.
  2. In the caffeine contractures, both the denervated and the innervated muscles showed similar sequential changes in the relative concentration of phosphocreatine (PCr) to β-adenosine triphosphate (β-ATP) and inorganic phosphate (Pi) to β-ATP. Instead, the intracellular pH value of the denervated muscle was lower than that of the control.
- 3.
  3. It is suggested that phosphate metabolism of the denervated muscle during contracture shows little difference from that of the control, nevertheless, the buffering capacity is decreased in the early stage of atrophy.
Molecular aspects of the trophic influence of nerve on muscle
1983, Progress in Neurobiology
Calcium content of rat fast and slow muscle after denervation
1981, Comparative Biochemistry and Physiology -- Part A: Physiology
- 1.
  1. Muscle weights and calcium contents after denervation were examined in rat extensor digitorum longus (EDL) and soleus (SOL) muscle.
- 2.
  2. An initial modest increase in EDL and SOL wet weight occurs following which atrophy to about 33% control weight occurs within one month.
- 3.
  3. Dry weight does not increase but begins to decrease on the second day after denervation.
- 4.
  4. EDL calcium content remains constant for the first ten days following which it decreases for two weeks then returns to control values.
- 5.
  5. SOL calcium content increased in the first two weeks then remains at control values.
- 6.
  6. Since calcium content remains constant but wet weight decreased markedly an apparent increase in calcium concentration occurs.
Denervation and developmental alterations of glycogen synthase and glycogen phosphorylase in mammalian skeletal muscle
1979, Experimental Neurology
The activities of glycogen synthase and glycogen phosphorylase were determined in normal and denervated fast and slow muscle and in developing skeletal muscle of the rabbit. Normal fast muscle (16.0 nmol glucose/min/mg) showed increased specific activity for glycogen synthase compared to slow muscle (9.5 nmol glucose/min/mg). Glycogen synthase in both muscle types was activated approximately twofold by 10 mm glucose 6-phosphate. After 7 days of denervation, glycogen synthase decreased 78% in both muscle types. Glycogen phosphorylase activity of fast muscle (1088 nmol P_i min/mg) was eightfold greater than slow muscle (141 nmol P_i/min/mg). Denervation resulted in a 33% decline in phosphorylase activity in fast muscle and 52% in slow muscle. Denervation had no effect on either fast or slow muscle glycogen content. Neonatal skeletal muscle exhibited relatively lower values of glycogen synthase (1.8 nmol glucose/min/mg) and glycogen phosphorylase (284 nmol P_i/min/mg) than adult muscle. Adult activity levels of each enzyme occurred at approximately the 4th postnatal week for glycogen synthase and the 6th postnatal week for glycogen phosphorylase. The data suggest, on a qualitative basis, that denervation induced a decrease in activity of key enzymes in glycogen metabolism similar to that observed in newborn skeletal muscle.

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¹: The authors are grateful to Mrs. Elaine Johnson for expert technical assistance in the analyses of substrate levels. This work was supported by U.S. Public Health Grants NB-08157 and NB-08233.

View full text

Effect of ischemia and denervation on metabolism of fast and slow mammalian skeletal muscle

Abstract

Exp. Neurol.

J. Biol. Chem.

Advan. Enzyme Regul.

Anal. Biochem.

Exp. Neurol.

Equilibrium constant of phosphoryl transfer from adenosine triphosphate to galactose in the presence of galactokinase

Biochem. J.

Major metabolic pathways for carbohydrate metabolism of voluntary skeletal muscle

Amer. J. Physiol.

Changes in the synthesis of glycogen during recovery of function of denervated and tenotomized muscles

Physiol. Bohemoslov.

Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses

J. Physiol. London

Carbohydrate metabolism in contracting dog skeletal muscle in situ

Amer. J. Physiol.

The metabolism of the tonic and tetanic muscles. I. Glycolytic metabolism

Arch. Biochem. Biophys.

Further investigations on the influence of motoneurones on the speed of muscle contraction

J. Physiol. London

“Trophic” influences of nerve on muscle

Physiol. Rev.

Metabolic reactibility of the denervated muscle

Succinate-cytochrome c reductase, cytochrome oxidase, and aldolase activities of denervated rat skeletal muscle

Amer. J. Physiol.

Relationships between energy reserves and the function in rat superior cervical ganglion

J. Neurochem.