Modification of motor units in fast twitch muscle after partial denervation [proceedings].
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Animals↗
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Blood flow and glucose uptake in denervated, insulin-resistant muscles.
To investigate whether changes in blood flow contribute to the insulin resistance in denervated muscles, basal and insulin-stimulated 2-deoxy-D-glucose (2-DG) uptake in vivo and blood flow were measured in soleus (slow twitch), plantaris (fast twitch), and gastrocnemius (fast twitch) muscles at 1 and 3 days after a right hindlimb denervation in the rat. Muscles of the contralateral sham hindlimb served as an internal control. Sham plantaris and gastrocnemius muscles showed 32 and 60% lower basal 2-DG uptake, 46 and 66% lower insulin-stimulated 2-DG uptake, and 79 and 81% lower blood flow, respectively, compared with sham soleus muscle. At 1 day after denervation, soleus, plantaris, and gastrocnemius muscles exhibited an 80, 64, and 42% decrease in insulin-stimulated 2-DG uptake, respectively, in the presence of 63, 323, and 304% higher blood flow, respectively. At 3 days after denervation, soleus muscle showed a 60% decrease in basal 2-DG uptake, complete unresponsiveness to insulin, and an 86% decrease in blood flow. In contrast, the denervated plantaris and gastrocnemius muscles exhibited a 262 and 105% increase in basal 2-DG uptake, respectively, no change in insulin-stimulated 2-DG uptake, and no change in blood flow compared with corresponding contralateral sham muscles. The results demonstrate that muscle blood flow is influenced by muscle fiber population and time after denervation and that changes in blood flow do not contribute to the insulin resistance in the denervated muscles.
Animals↗
Comparison of oblique versus hockey-stick surgical incision for kidney transplantation.
The hockey-stick surgical incision is becoming more popular than the oblique incision for kidney transplantations. Both incisions are convenient and comfortable. Both have some drawbacks, such as muscle denervation for the former, or section of lateral muscles for the latter. In this retrospective study, we compared these incisions with regard to the incidence of long-term complications, such as postincisional hernia, relaxation of the abdominal wall, and a poor cosmetic result. One hundred patients (50 of each type) were evaluated at an average of 4.5 years after transplantation (3 months-15 years). Occurrence of incisional hernia was 16% in the former (8 cases) versus 4% in the latter (2 cases: X(2) = 4; P < .05). A major relaxation of the abdominal wall was found in 24% of the former (12 cases) versus 8% of the latter (4 cases) (X(2) = 4.76; P < .05). These complications were not correlated with age, sex, weight, side of transplant, or immunosuppressive drugs. In the former patients with hockey-stick incisions, the overall cosmetic results were poor, because in most cases the incision had been prolonged upward, above the transverse umbilical line, even as high as the costal arch. In 20% of the former patients with hockey-stick incisions, the scar had widened, particularly in the upper vertical branch of the J incision. We conclude that the final outcome of the oblique surgical incision was better than the hockey-stick incision because of the lower incidence of hernia and abdominal wall relaxation and the more favorable cosmetic results.
Denervation↗
Neural influence on protein kinase C isoform expression in skeletal muscle.
Protein kinase C (PKC) is a family of enzymes involved in synapse formation and signal transduction at the neuromuscular junction. Two PKC isoforms, classical PKC alpha and novel PKC theta, have been shown to be enriched in skeletal muscle or localized to the endplate. We examined the role of nerve in regulating the expression of these PKC isoforms in rat skeletal muscle by denervating diaphragm muscle and measuring PKC protein expression at various postoperative times. nPKC theta protein levels decreased 65% after denervation, whereas cPKC alpha levels increased 80% compared with control hemidiaphragms. These results suggest that innervation regulates PKC theta and alpha isoform expression in skeletal muscle. To explore further how nerve regulates PKC expression, we characterized PKC isoform expression in rat myotubes deprived of neural input. Myoblast expression of nPKC theta was low, and the increase in nPKC theta expression that occurred during differentiation into myotubes resulted in levels of nPKC theta significantly below adult skeletal muscle. cPKC alpha expression in myoblastic increased during differentiation to levels that exceeded expression in adult skeletal muscle. Coculturing myotubes within neuroblastoma X glioma hybrid clonal cell line (NG108-15) increased nPKC theta expression, but not cPKC alpha, suggesting that nPKC theta in skeletal muscle and myotubes is regulated by nerve contact or by a factor(s) provided by nerve. Treating myotubes with tetrodotoxin did not affect either basal- or NG108-15 cell-stimulated nPKC theta expression. Together these results suggest that expression of nPKC theta in skeletal muscle is regulated by a transynaptic interaction with nerve that specifically influences nPKC theta expression.
Animals↗
Myosin light and heavy chains in rat gastrocnemius and diaphragm muscles after chronic denervation or reinnervation.
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Animals↗
Epaxial muscle function during locomotion in a lizard (Varanus salvator) and the proposal of a key innovation in the vertebrate axial musculoskeletal system
The pattern of electromyographic activity in the epaxial muscles of walking and running lizards (water monitors, Varanus salvator) was quantified with high-speed video and synchronized electromyography. Muscle denervation experiments were performed and ground reaction forces were recorded to evaluate hypotheses of muscle function. Water monitors exhibit unilateral, uniphasic activation of the epaxial muscles ipsilateral to rear limb support. The iliocostalis and longissimus dorsi muscles are active throughout the support phase of the rear limb, while the transversospinalis is active only during the second half of the support phase. The timing of muscle activity does not support the presumed locomotor function of the epaxial muscles of lizards (lateral bending of the trunk). Bilateral denervation of the two most lateral epaxial muscles (iliocostalis and longissimus dorsi) caused no significant change in the amplitude of lateral trunk bending. These two epaxial muscles do not appear to be necessary for lateral bending of the trunk, nor do they appear to be involved in resisting lateral bending of the trunk. On the basis of the data reported in this study, as well as a re-evaluation of previously existing data, it is proposed that the locomotor function of the epaxial muscles of lizards is to stabilize the trunk against the vertical component of the ground reaction forces; i.e. the epaxial muscles function in a postural role during locomotion in lizards, as they do in other amniotes. This proposed postural role of the epaxial muscles may represent a key innovation of amniotes, made possible by the loss of an aquatic larval stage in their common ancestor.
Journal Article↗
[Effect of disruption of chloride conductance on the development of denervation changes in muscle fiber membranes of the rat].
A decrease in resting MP, increase in the input resistance, appearance of anode breakdown APs, and extrajunctional acetylcholine sensitivity following denervation were revealed in the rat diaphragm muscle fibres. Addition of 1 X 10(-4) M furosemide to the culture medium reduced the degree of post-denervation muscle membrane depolarization and of extrajunctional acetylcholine sensitivity, but did not prevent the changes in passive electrical properties and in firing level of the muscle fibre membrane. Chloride ions could serve as intracellular messengers responsible for the neurotrophic control of muscle membrane resting potential and membrane sensitivity to acetylcholine. The Cl- are not essential in neurotrophic regulation of the electrogenic properties of membrane.
Acetylcholine↗
Partial peripheral motor nerve lesions induce changes in the conduction properties of remaining intact motoneurons.
A partial injury or loss of peripheral motor axons is followed by compensatory sprouting of remaining intact motor axons in order to reinnervate muscle. Little is known, however, about the electrophysiologic properties proximally of these intact motoneurons and their axons following injury of neighboring motor axons. We studied the conduction properties of intact cat motor axons and motoneurons proximal to the site of a partial peripheral nerve section. Twelve weeks after the partial transection of the cat medial gastrocnemius motor nerve, there was a significant (7%) reduction in conduction velocity and a 13% prolongation in afterhyperpolarization half-decay time in the remaining intact motoneurons, compared with controls. Partial injury to motor nerves thus induces reactive electrophysiologic changes in the remaining intact motoneurons and their axons, perhaps associated with compensatory sprouting within partially denervated muscle.
Action Potentials↗
Abnormal fatty acid metabolism in childhood spinal muscular atrophy.
Our previous experience with abnormal fatty acid metabolism in several children with spinal muscular atrophy (SMA) prompted evaluation of fatty acid metabolism in a larger cohort. Thirty-three infants with severe infantile SMA were shown to have a significantly increased ratio of dodecanoic to tetradecanoic acid in plasma compared with normal infants and 6 infants affected with equally debilitating, non-SMA denervating disorders. Seventeen children with milder forms of SMA had normal fatty acid profiles. In addition, all 5 infants with severe SMA evaluated in a fasting state developed a distinctive and marked dicarboxylic aciduria, including saturated, unsaturated, and 3-hydroxy forms, comparable in severity with the dicarboxylic aciduria of children with primary defects of mitochondrial fatty acid beta-oxidation. Nine children with chronic SMA and 23 control patients did not develop an abnormal dicarboxylic aciduria during fasting. No known disorder of fatty acid metabolism explains all of the abnormalities we find in SMA. Our data suggest, however, that the abnormalities are not a consequence of SMA-related immobility, systemic illness, muscle denervation, or muscle atrophy. These abnormalities in fatty acid metabolism may be caused by changes in cellular physiology related to the molecular defects of the SMA-pathogenic survival motor neuron gene or neighboring genes.
Age Distribution↗
[Possible participation of cyclic AMP in regulating acid hydrolase activity in muscle tissue in avitaminosis E and denervation].
In the muscles of denervated and vitamin E-deficient rabbits the level of 3', 5'-cyclic AMP proved to decrease with a simultaneous increase in the activity of cAMP phosphodiesterase. In vivo experiments showed that at the concentration of 10(-4) cAMP was capable of retarding the release of acid phosphatase from the lysosome-rich fraction obtained from the muscles of E-deficient rabbits. Thus, in muscular dystrophy elevation of acid hydrolase activity in the skeletal muscle was due to leakage of the enzymes from the lysosomes as a result of decreased lysosome membrane stability because of decreased cAMP level.
3',5'-Cyclic-AMP Phosphodiesterases↗
Factors in the inactivation of postjunctional membrane receptors of frog skeletal muscle.
Several factors which influence the rate of inactivation of muscle postjunctional membrane (PJM) receptors during the sustained application of carbamylcholine (CARB) have been studied by two methods. The rate of inactivation was increased by elevating the tonicity of the bathing medium, by increasing the CARB concentration, by raising the calcium ion concentration, and by substituting SO(4) (=) for Cl(-) ions in the extracellular fluid. The relative effectiveness of calcium and other divalent cations in receptor inactivation was compared. In the absence of calcium, other divalent cations such as magnesium, strontium, or manganese were not efficient substitutes for calcium. In the presence of calcium, the addition of strontium or manganese ions accelerated the rate of receptor inactivation, but the addition of magnesium (up to 12 mM) inhibited this process. The inactivation of the membrane receptors in denervated muscle fibers was found to be similar to that in innervated muscle fibers. Various factors in PJM receptor inactivation are discussed. It is suggested that PJM receptor inactivation is influenced by the binding of calcium ions to sites on the internal surface of the PJM.
Acetylcholine↗
Role of innervation, excitability, and myogenic factors in the expression of the muscular chloride channel ClC-1. A study on normal and myotonic muscle.
The muscular chloride channel (ClC-1) is essential for a normal excitability of mature mammalian muscle fibers; inactivation of the corresponding gene by mutations leads to hyperexcitability of muscle, the hallmark of the disease myotonia. In the mouse, there is very little ClC-1 mRNA in myotubes, and its concentration increases steeply during postnatal development, suggesting a role of the motor nerve in ClC-1 expression. We investigated the response of the expression of the corresponding gene Clc-1 to different patterns of muscle activity as controlled by sarcolemmal excitability and by innervation. In rat and mouse, the level of ClC-1 mRNA was higher in fast (extensor digitorum longus) than in slow (soleus) muscle. Myotonia in the ADR mouse is caused by an insertional mutation leading to the adr allele of the Clc-1 gene and to grossly abnormal ClC-1 mRNAs. Nevertheless, in +/adr heterozygous, phenotypically wild type (WT) animals, the expression levels of both alleles correspond to the gene dosage. However, in the myotonic ADR mouse in which both Clc-1 genes are defective, ClC-1 mRNA levels in slow muscle were nearly as high as in WT fast muscle. In WT muscle, denervation within 2 days caused a drastic reduction of the ClC-1 mRNA level and at the same time an increase of myogenin and MyoD mRNAs. Neither effect of denervation was observed in myotonic mice (homozygous for the alleles adr or adrK), suggesting that spontaneous electrical activity of the hyperexcitable sarcolemma may substitute for nerve activity. Furthermore, potential MyoD/myogenin-binding sequence motifs were identified in the 5' regulatory region of the Clc-1 gene. These findings suggest that the activity-dependent regulation of the muscular chloride channel 1 gene is mediated by myogenic factors.
Amino Acid Sequence↗
AMP kinase is not required for the GLUT4 response to exercise and denervation in skeletal muscle.
An acute bout of exercise increases muscle GLUT4 mRNA in mice, and denervation decreases GLUT4 mRNA. AMP-activated protein kinase (AMPK) activity in skeletal muscle is also increased by exercise, and GLUT4 mRNA is increased in mouse skeletal muscle after treatment with AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside(AICAR). These findings suggest that AMPK activation might be responsible for the increase in GLUT4 mRNA expression in response to exercise. To investigate the role of AMPK in GLUT4 regulation in response to exercise and denervation, transgenic mice with a mutated AMPK alpha-subunit (dominant negative; AMPK-DN) were studied. GLUT4 did not increase in AMPK-DN mice that were treated with AICAR, demonstrating that muscle AMPK is inactive. Exercise (two 3-h bouts of treadmill running separated by 1 h of rest) increased GLUT4 mRNA in both wild-type and AMPK-DN mice. Likewise, denervation decreased GLUT4 mRNA in both wild-type and AMPK-DN mice. GLUT4 mRNA was also increased by AICAR treatment in both the innervated and denervated muscles. These data demonstrate that AMPK is not required for the response of GLUT4 mRNA to exercise and denervation.
Aminoimidazole Carboxamide↗
[The influence of caldesmon on strong binding of myosin with actin in denervated rat skeletal muscles].
The effect of caldesmon (CaD) on conformational changes in F-actin modified by fluorescent probe TRITC-phalloidin was investigated by polarized fluorimetry. Changes were induced by a subfragment-1 (S-1) of myosin in the absence or presence of CaD in ghost muscle fibers obtained from intact and denervated slow (SOL) and fast (EDL) skeletal muscles of rats. S-1 binding to actin of both SOL and EDL muscles was shown to cause changes in polarized parameters of TRITC-phalloidin typical for a strong actin-myosin binding as well as of transition ofactin subunits from "off" to "on" state. CaD inhibits this significantly. Denervation atrophy inhibits the effect of S-1 as well but does not affect the capability of CaD decreasing the formation of strong binding in actomyosin complex. It is supposed that CaD "freezes" F-actin structure in "off" state. The denervation atrophy has no effect on CaD responsibility to bind thin filaments and to switch "off" actin monomers.
Actins↗
Effect of hypothermia on the twitch and tetanic contractions of denervated rat diaphragm muscle under isotonic conditions.
Effect of hypothermia was studied on the twitch and tetanic contractions of the chronically denervated rat diaphragm muscles under isotonic conditions. The muscles were denervated for 15-20 days and the temperature was lowered from 35 degrees C to 15 degrees C. The results showed that hypothermia and chronic denervation had very little effect on the isotonic contraction parameters since these were found to be unaltered at all temperatures except at 15 degrees C. It is suggested that denervation has no significant effect on the contractile component of our experimental muscles.
Journal Article↗
Ultrastructural and cytochemical features of mammalian skeletal muscle fibres following denervation.
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Animals↗
Alterations in the functional properties of skinned fibers from denervated rabbit skeletal muscle.
Isometric tension was recorded in vitro from chemically skinned fibers obtained from normal and 14-day-denervated extensor digitorum longus muscles of the rabbit. Denervation potentiated the tensions elicited by pCa 6.0 but did not modify the pCa value (5.6) required for maximum tension. Ca2+ transport across the membranes of the sarcoplasmic reticulum (SR) was markedly affected by denervation. Thus the rate of ATP-dependent net Ca2+ uptake increased significantly, and the spontaneous release ("leakage") of the Ca2+ stored in the SR was significantly reduced in denervated fibers. These effects lead to increased accumulation of Ca2+ in the lumen of the SR. The dose-response curve for the halothane-induced contractures of Ca2(+)-loaded skinned fibers was displaced to the left after denervation. Thus 0.7 mM halothane, a concentration that elicited no tension in 10 control fibers, induced contractures in the 10 denervated fibers tested. The potentiation of the halothane-induced tensions is attributed mainly to the larger stores of Ca2+ in the SR of denervated fibers. The possibility that denervation may also affect the interaction of halothane with the SR membranes is discussed.
Adenosine Triphosphate↗
Effects of chronic electrical stimulation on contractile properties of long-term denervated rat skeletal muscle.
1. The contractile properties of fast-twitch (extensor digitorum longus or EDL) and slow-twitch (soleus) muscles in the rat were followed for periods of between 4 and 10 months after denervation. The effects of chronic electrical stimulation during the last 3-8 weeks of denervation were investigated. 2. The fall in tetanic tension that follows axotomy ended after about 4 months' denervation. The equilibrium tension was about 0.75% of control tension in EDL and 0.2-0.3% in soleus. 3. The low tension in soleus was due partly to the small diameter of the muscle fibres (atrophy) and partly to their necrosis that resulted in an 8-fold fall in specific tension (the force per unit cross-sectional area). Similar but less extreme changes occurred in EDL. 4. It is speculated that the final level of tension reached by unstimulated denervated muscles is an equilibrium between decrease in force due to atrophy and necrosis and increase due to regeneration. Differences between the final tension levels in soleus and EDL cannot be accounted for quantitatively by known differences in atrophy alone. Therefore, the rate of necrosis in soleus and of regeneration in EDL may be higher. 5. Chronic stimulation of long-term denervated muscle increased force generation by about 7-fold in EDL and between 20 and 55 times in soleus. The final tension reached was between 4 and 5% of normal in both muscles. Specific tension of fibres was almost completely restored by stimulation and the number of fibres was normal. The failure to recover full tension was largely due to failure to reverse denervation atrophy completely. 6. Twitch contraction and relaxation times were identical in denervated-stimulated soleus and EDL. There was no evidence for dependence on duration of stimulation or tension of the muscle. The normalized maximum rate of rise of tetanic tension remained higher in EDL than soleus.
Animals↗