Studies of the halothane-cooling contractures of skeletal muscle

1987 ◽  
Vol 65 (4) ◽  
pp. 697-703 ◽  
Author(s):  
Roberto T. Sudo ◽  
Gisele Zapata ◽  
Guilherme Suarez-Kurtz

The characteristics of transient contractures elicited by rapid cooling of frog or mouse muscles perfused in vitro with solutions equilibrated with 0.5–2.0% halothane are reviewed. The data indicate that these halothane-cooling contractures are dose dependent and reproducible, and their amplitude is larger in muscles containing predominantly slow-twitch type fibers, such as the mouse soleus, than in muscles in which fast-twitch fibers predominate, such as the mouse extensor digitorum longus. The halothane-cooling contractures are potentiated in muscles exposed to succinylcholine. The effects of Ca2+-free solutions, of the local anesthetics procaine, procainamide, and lidocaine, and of the muscle relaxant dantrolene on the halothane-cooling contractures are consistent with the proposal that the halothane-cooling contractures result from synergistic effects of halothane and low temperature on Ca sequestration by the sarcoplasmic reticulum. Preliminary results from skinned rabbit muscle fibers support this proposal. The halothane concentrations required for the halothane-cooling contractures of isolated frog or mouse muscles are comparable with those observed in serum of patients during general anesthesia. Accordingly, fascicles dissected from muscle biopsies of patients under halothane anesthesia for programmed surgery develop large contractures when rapidly cooled. The amplitude of these halothane-cooling contractures declined with the time of perfusion of the muscle fascicles in vitro with halothane-free physiological solutions. It is suggested that the halothane-cooling contractures could be used as a simple experimental model for the investigation of the effects of halothane on Ca homeostasis and contractility in skeletal muscle and for study of drugs of potential use in the management of the contractures associated with the halothane-induced malignant hyperthermia syndrome. It is shown that salicylates, but not indomethacin or mefenamic acid, inhibit the halothane-cooling contractures.

1994 ◽  
Vol 76 (4) ◽  
pp. 1753-1758 ◽  
Author(s):  
A. Bonen ◽  
D. A. Homonko

In the present study, we investigated the hypotheses that 1) skeletal muscle glyconeogenesis will increase after exercise, 2) greater changes in glyconeogenesis will be observed after exercise in fast-twitch muscles than in slow-twitch muscles, and 3) glycogen repletion will reduce the rates of glyconeogenesis. Mouse soleus and extensor digitorum longus (EDL) glycogen depots were reduced to the same levels by treadmill exercise (60 min) or epinephrine injection (75 micrograms/100 g body wt ip). Untreated animals were used as controls. We were able to prevent glycogen repletion by incubating muscles in vitro with sorbitol (75 mM) and to increase glycogen concentrations in vitro by incubating muscles with glucose (75 mM). The experimental results showed that glyconeogenesis was increased by exercise (EDL, +51%; soleus, +82%) when glycogen levels were kept low. When glycogen depots were increased, the rate of glyconeogenesis was lowered in the exercised EDL (P < 0.05) but not in the soleus (P > 0.05). Reductions in muscle glycogen by epinephrine did not change the rate of glyconeogenesis in EDL, either when glycogen depots were kept low or were repleted (P > 0.05). In contrast, in the soleus, epinephrine-induced reductions in glycogen did stimulate glyconeogenesis (P < 0.05). Analyses in EDL showed that in nonexercised muscles glycogen concentrations were minimally effective in altering the rates of glyconeogenesis. A 30% decrement in glycogen increased glyconeogenesis by 5% in resting muscles, whereas the same decrement increased glyconeogenesis by 51% in exercised muscles.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 340 (3) ◽  
pp. 657-669 ◽  
Author(s):  
Rosa I. VINER ◽  
Deborah A. FERRINGTON ◽  
Todd D. WILLIAMS ◽  
Diana J. BIGELOW ◽  
Christian SCHÖNEICH

The accumulation of covalently modified proteins is an important hallmark of biological aging, but relatively few studies have addressed the detailed molecular-chemical changes and processes responsible for the modification of specific protein targets. Recently, Narayanan et al. [Narayanan, Jones, Xu and Yu (1996) Am. J. Physiol. 271, C1032-C1040] reported that the effects of aging on skeletal-muscle function are muscle-specific, with a significant age-dependent change in ATP-supported Ca2+-uptake activity for slow-twitch but not for fast-twitch muscle. Here we have characterized in detail the age-dependent functional and chemical modifications of the rat skeletal-muscle sarcoplasmic-reticulum (SR) Ca2+-ATPase isoforms SERCA1 and SERCA2a from fast-twitch and slow-twitch muscle respectively. We find a significant age-dependent loss in the Ca2+-ATPase activity (26% relative to Ca2+-ATPase content) and Ca2+-uptake rate specifically in SR isolated from predominantly slow-twitch, but not from fast-twitch, muscles. Western immunoblotting and amino acid analysis demonstrate that, selectively, the SERCA2a isoform progressively accumulates a significant amount of nitrotyrosine with age (≈ 3.5±0.7 mol/mol of SR Ca2+-ATPase). Both Ca2+-ATPase isoforms suffer an age-dependent loss of reduced cysteine which is, however, functionally insignificant. In vitro, the incubation of fast- and slow-twitch muscle SR with peroxynitrite (ONOO-) (but not NO/O2) results in the selective nitration only of the SERCA2a, suggesting that ONOO- may be the source of the nitrating agent in vivo. A correlation of the SR Ca2+-ATPase activity and covalent protein modifications in vitro and in vivo suggests that tyrosine nitration may affect the Ca2+-ATPase activity. By means of partial and complete proteolytic digestion of purified SERCA2a with trypsin or Staphylococcus aureus V8 protease, followed by Western-blot, amino acid and HPLC-electrospray-MS (ESI-MS) analysis, we localized a large part of the age-dependent tyrosine nitration to the sequence Tyr294-Tyr295 in the M4-M8 transmembrane domain of the SERCA2a, close to sites essential for Ca2+ translocation.


2009 ◽  
Vol 2009 ◽  
pp. 1-16 ◽  
Author(s):  
M. Zimowska ◽  
A. Duchesnay ◽  
P. Dragun ◽  
A. Oberbek ◽  
J. Moraczewski ◽  
...  

When injured by crushing, the repair of the slow-twitch soleus rat muscle, unlike the fast-twitch EDL, is associated with fibrosis. As TGFβ1, whose activity can be controlled by glycosaminoglycans (GAG), plays a major role in fibrosis, we hypothesized that levels of TGFβ1 and GAG contents could account for this differential quality of regeneration. Here we show that the regeneration of the soleus was accompanied by elevated and more sustained TGFβ1 level than in the EDL. Neutralization of TGFβ1 effects by antibodies to TGFβ1 or its receptor TGFβ-R1 improved muscle repair, especially of the soleus muscle, increased in vitro growth of myoblasts, and accelerated their differentiation. These processes were accompanied by alterations of GAG contents. These results indicate that the control of TGFβ1 activity is important to improve regeneration of injured muscle and accelerate myoblast differentiation, in part through changes in GAG composition of muscle cell environment.


2011 ◽  
Vol 110 (3) ◽  
pp. 820-825 ◽  
Author(s):  
Robyn M. Murphy

Human physiological studies typically use skeletal muscle biopsies from the heterogeneous vastus lateralis muscle comprised of both fast-twitch and slow-twitch fiber types. It is likely that potential changes of physiological importance are overlooked because fiber-type specific responses may not be apparent in the whole muscle preparation. A technological advance in Western blotting is presented where proteins are analyzed in just one small segment (<2 mm) of individual fibers dissected from freeze-dried muscle samples using standard laboratory equipment. A significant advance is being able to classify every fiber at the level of both contractile (myosin heavy chain and tropomyosin) and sarcoplasmic reticulum [sarco(endo)plasmic reticulum Ca2+-ATPase type 1] properties and then being able to measure specific proteins in the very same segments. This removes the need to fiber type segments before further analyses and, as such, dramatically reduces the time required for sample collection. Compared with slow-twitch fibers, there was less AMP-activated protein kinase (AMPK)-α1 (∼25%) and AMPK-β1 (∼60%) in fast-twitch fibers from human skeletal muscle biopsies.


1986 ◽  
Vol 250 (6) ◽  
pp. C813-C820 ◽  
Author(s):  
D. A. Young ◽  
M. M. Chi ◽  
O. H. Lowry

This study was made to test the validity of a simple biopsy technique for assessing the metabolic capacity of skeletal muscle. The biopsy is stimulated under mineral oil without attachment, i.e., without load or tension, then freeze-clamped and assayed for ATP, phosphocreatine, glucose 6-phosphate, and lactate. The mineral oil creates a closed anaerobic system. Background studies demonstrated in the absence of a load, metabolic changes with stimulation were little affected by cutting the fibers to obtain the biopsy; and high-energy phosphate (approximately P) consumption during a brief tetanus was not much lower than that for an isometric tetanus. Individual fast-twitch oxidative-glycolytic (IIA) and fast-twitch glycolytic (IIB) fibers obtained from the freeze-clamped biopsy showed distinct differences in approximately P consumption and metabolic changes. The results indicate that this technique could be useful for studies of normal and pathological human muscle.


1994 ◽  
Vol 19 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Arend Bonen ◽  
Karl J. A. McCullagh

Skeletal muscle lactate transport was investigated in vitro in isolated fast-twitch (EDL) and slow-twitch soleus (Sol) skeletal muscles from control and exercised mice. Exercise (23 m/min, 8% grade) reduced muscle glycogen by 37% in EDL (p < 0.05) and by 35% in Sol muscles (p < 0.05). Lactate transport measurements (45 sec) were performed after 60 min of exercise in intact EDL and Sol muscles in vitro, at differing pH (6.5 and 7.4) and differing lactate concentrations (4 and 30 mM). Lactate transport was observed to be greater in Sol than in EDL (p < 0.05). In the exercised muscles there was a small but significant increase in lactate transport (p < 0.05). Lactate transport was greater when exogenous lactate concentrations were greater (p < 0.05) and more rapid at the lower pH (p < 0.05). These studies demonstrated that lactate transport was increased with exercise. Key words: soleus, EDL, treadmill exercise


1985 ◽  
Vol 248 (5) ◽  
pp. C406-C409 ◽  
Author(s):  
D. A. Young ◽  
H. Wallberg-Henriksson ◽  
J. Cranshaw ◽  
M. Chen ◽  
J. O. Holloszy

The effect of catecholamines on glycogenolysis and sugar transport was evaluated in rat epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles in vitro. When muscles were incubated with 0.1 microM epinephrine (both an alpha- and beta-agonist), the proportion of phosphorylase in the a form increased from 6.2 +/- 0.7 to 37.4 +/- 5.7% in epitrochlearis muscle and from 9.1 +/- 0.7 to 21.6 +/- 1.3% in soleus muscle. Both the activation of phosphorylase and the resulting glycogenolysis could be prevented by preincubation with the beta-blocker, propranolol. The effect of catecholamines on the rate of sugar transport was also examined in epitrochlearis muscle. The beta-agonist, isoproterenol, significantly depressed the rate of 3-O-methylglucose uptake, while the alpha-agonist, phenylephrine, had no effect. Inclusion of 0.1% albumin in the incubation medium increased the resting rate of sugar transport twofold. When isoproterenol + albumin were present, rather than exerting a depressive effect the catecholamine further increased the rate of sugar uptake. This increase was prevented by preincubation with propranolol. It was concluded that glycogenolysis and sugar transport in rat skeletal muscle are solely under beta-adrenergic control.


1996 ◽  
Vol 270 (1) ◽  
pp. C76-C85 ◽  
Author(s):  
P. C. Tullson ◽  
K. W. Rundell ◽  
R. L. Sabina ◽  
R. L. Terjung

Dietary supplementation of the creatine analogue beta-guanidinopropionic acid (beta-GPA) decreases in vitro skeletal muscle AMP deaminase (AMP-D) activity in rats. Downregulation of AMP-D activity was progressive and greater in fast-twitch muscles (70-80%) than in the slow-twitch soleus muscle (approximately 50%). The loss in AMP-D activity had little effect on inosine 5'-monophosphate accumulation in mixed-fiber muscle with intense tetanic contractions. In contrast, inosine 5'-monophosphate formation was evident earlier in fast-twitch red and white fiber sections of creatine-depleted animals during intense twitch contractions, indicating that fast-twitch muscle of beta-GPA-treated rats buffers decreases in the ATP/ADPfree ratio via deamination, even though AMP-D activity is less. Isoforms of skeletal muscle AMP-D mRNAs in mixed-fiber muscle were not altered by feeding beta-GPA for up to 9 wk. Creatine depletion did not alter total immunoreactivity; however, a redistribution of AMP-D immunoreactivity from primarily an approximately 80-kDa form toward lower apparent molecular mass species (approximately 60 and approximately 56 kDa) was observed. Posttranslational changes in AMP-D appear related to changes in activity.


1990 ◽  
Vol 258 (4) ◽  
pp. E693-E700 ◽  
Author(s):  
A. Bonen ◽  
J. C. McDermott ◽  
M. H. Tan

We examined the effects of selected hormones and pH on the rates of glyconeogenesis (L-[U-14C]-lactate----glycogen) and glycogenesis (D-[U-14C]glucose----glycogen) in mouse fast-twitch (FT) and slow-twitch muscles incubated in vitro (37 degrees C). Glyconeogenesis and glycogenesis increased linearly with increasing concentrations of lactate (5-20 mM) and glucose (2.5-10 mM), respectively, in both muscles. Glyconeogenesis was approximately three- to fourfold greater in the extensor digitorum longus (EDL) than in the soleus, whereas basal glycogenesis was twofold greater in the soleus muscle than in the EDL. Lactate accounted for up to 5% of the glycogen formed in the soleus and up to 32% in the EDL relative to the rates of glycogenesis (i.e., 5 mM glucose + 10 nM insulin) in each muscle. Corticosterone (10(-12)-10(-6) M) failed to alter glyconeogenesis, whereas this hormone reduced glycogenesis. Insulin (10 nM) markedly stimulated glycogenesis but failed to stimulate glyconeogenesis. The rates of both glycogenesis and glyconeogenesis were pH sensitive, with optimal rates at pH 6.5-7.0 in both muscles. Glyconeogenesis increased by 49% in the soleus and by 39% EDL at pH 6.5 compared with pH 7.4. Glycogenesis increased in the soleus (SOL) and EDL in the absence (SOL: +22%; EDL: +52%) and presence of insulin (SOL: +22%; EDL: +51%) at pH 6.5 when compared with pH 7.4. In additional experiments with the perfused rat hindquarter, rates of glyconeogenesis were shown to be highly correlated with proportion of FT muscle fibers in a muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


1980 ◽  
Vol 238 (6) ◽  
pp. E518-E523 ◽  
Author(s):  
H. Kaciuba-Uscilko ◽  
G. A. Dudley ◽  
R. L. Terjung

The influence of thyroid status on the clearance of chylomicron 14C-labeled triglycerides (14C-TG), the fractional uptake of 14C-TG, and activity of lipoprotein lipase (LPL) in the different skeletal muscle fiber types was evaluated in pentobarbital-anesthetized rats. The turnover of plasma TG was approximately fourfold greater in the hyperthyroid (HyperT) compared to either euthyroid (EUT) or hypothyroid (HypoT) animals. The uptake of 14C-TG was increased in slow-twitch red and fast-twitch red muscle sections of the HyperT group and normal in the HypoT group. The changes in LPL activity in these two fiber types were inversely related to thyroid influence, with decreases found in the HyperT group and increases found in the HypoT group. Thus, the uptake of 14C-TG in these high-oxidative fibers, relative to the LPL activity, varied directly with thyroid influence. As a result, the normal linear relationship, apparent for the different types of skeletal muscle, between LPL activity measured in vitro and TG uptake determined in situ was not maintained.


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