Metabolic responses from rest to steady state determine contractile function in ischemic skeletal muscle

1997 ◽  
Vol 273 (2) ◽  
pp. E233-E238 ◽  
Author(s):  
J. A. Timmons ◽  
S. M. Poucher ◽  
D. Constantin-Teodosiu ◽  
I. A. Macdonald ◽  
P. L. Greenhaff
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Muscle Contraction ◽  
Metabolic Response ◽  
Contractile Function ◽  
Pyruvate Dehydrogenase Complex ◽  
Force Production ◽  
Critical Factor ◽  
Control Group ◽  
State Force

Skeletal muscle contraction during ischemia, such as that experienced by peripheral vascular disease patients, is characterized by rapid fatigue. Using a canine gracilis model, we tested the hypothesis that a critical factor determining force production during ischemia is the metabolic response during the transition from rest to steady state. Dichloroacetate (DCA) administration before gracilis muscle contraction increased pyruvate dehydrogenase complex activation and resulted in acetylation of 80% of the free carnitine pool to acetylcarnitine. After 1 min of contraction, phosphocreatine (PCr) degradation in the DCA group was approximately 50% lower than in the control group (P < 0.05) during conditions of identical force production. After 6 min of contraction, steady-state force production was approximately 30% higher in the DCA group (P < 0.05), and muscle ATP, PCr, and glycogen degradation and lactate accumulation were lower (P < 0.05 in all cases). It appears, therefore, that an important determinant of contractile function during ischemia is the mechanisms by which ATP regeneration occurs during the period of rest to steady-state transition.

Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction

1998 ◽  
Vol 274 (5) ◽  
pp. R1384-R1389 ◽  
Author(s):  
James A. Timmons ◽  
Simon M. Poucher ◽  
Dumitru Constantin-Teodosiu ◽  
Ian A. Macdonald ◽  
Paul L. Greenhaff
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Pyruvate Dehydrogenase Complex ◽  
Substrate Oxidation ◽  
Carbohydrate Oxidation ◽  
Control Group ◽  
Acetyl Coa ◽  
Glucose Fatty Acid Cycle ◽  
State Contraction ◽  
Activation Status

Pyruvate dehydrogenase complex (PDC) activation status has been described as being central in the regulation of tissue substrate oxidation as outlined by the glucose fatty-acid cycle. In the present study we examined the effects of reduced lipolysis, with use of nicotinate, and increased PDC activation, with use of dichloroacetate (DCA), on substrate utilization during 20 min of submaximal steady-state contraction (∼80% of maximal O2uptake) in canine gracilis skeletal muscle. At rest, PDC activation was unchanged by nicotinate but was ∼2.5-fold higher in the DCA group than in the control group ( P < 0.05). During contraction, PDC activation status increased to 3.5 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the control group, remained at 4.5 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the DCA group, but only increased to 2.2 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the nicotinate group ( P< 0.05). However, the estimated amount of carbohydrate oxidized during the 20-min contraction was similar across groups and did not follow the degree of PDC activation (81.2 ± 22.9, 95.9 ± 11.7, and 89.3 ± 18.9 mmol glucosyl units/kg dry muscle for control, nicotinate, and DCA, respectively). Thus it would appear that, during steady-state contraction, PDC activation status does not determine the rate of carbohydrate oxidation in skeletal muscle.

scholarly journals Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Julien S. Baker ◽  
Marie Clare McCormick ◽  
Robert A. Robergs
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Metabolic Response ◽  
Force Production ◽  
Energy Systems ◽  
Motor Units ◽  
Fold Increase ◽  
Metabolic Energy ◽  
Intense Exercise ◽  
Atp Regeneration

High-intensity exercise can result in up to a 1,000-fold increase in the rate of ATP demand compared to that at rest (Newsholme et al., 1983). To sustain muscle contraction, ATP needs to be regenerated at a rate complementary to ATP demand. Three energy systems function to replenish ATP in muscle: (1) Phosphagen, (2) Glycolytic, and (3) Mitochondrial Respiration. The three systems differ in the substrates used, products, maximal rate of ATP regeneration, capacity of ATP regeneration, and their associated contributions to fatigue. In this exercise context, fatigue is best defined as a decreasing force production during muscle contraction despite constant or increasing effort. The replenishment of ATP during intense exercise is the result of a coordinated metabolic response in which all energy systems contribute to different degrees based on an interaction between the intensity and duration of the exercise, and consequently the proportional contribution of the different skeletal muscle motor units. Such relative contributions also determine to a large extent the involvement of specific metabolic and central nervous system events that contribute to fatigue. The purpose of this paper is to provide a contemporary explanation of the muscle metabolic response to different exercise intensities and durations, with emphasis given to recent improvements in understanding and research methodology.

Phosphorylation of the regulatory light chains of myosin affects Ca2+sensitivity of skeletal muscle contraction

2002 ◽  
Vol 92 (4) ◽  
pp. 1661-1670 ◽  
Author(s):  
Danuta Szczesna ◽  
Jiaju Zhao ◽  
Michelle Jones ◽  
Gang Zhi ◽  
James Stull ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Muscle Contraction ◽  
Muscle Fibers ◽  
Light Chains ◽  
Regulatory Light Chains ◽  
Force Development ◽  
Skeletal Muscle Contraction ◽  
State Force ◽  
Kinetics Of

The role of phosphorylation of the myosin regulatory light chains (RLC) is well established in smooth muscle contraction, but in striated (skeletal and cardiac) muscle its role is still controversial. We have studied the effects of RLC phosphorylation in reconstituted myosin and in skinned skeletal muscle fibers where Ca2+sensitivity and the kinetics of steady-state force development were measured. Skeletal muscle myosin reconstituted with phosphorylated RLC produced a much higher Ca2+sensitivity of thin filament-regulated ATPase activity than nonphosphorylated RLC (change in −log of the Ca2+concentration producing half-maximal activation = ∼0.25). The same was true for the Ca2+sensitivity of force in skinned skeletal muscle fibers, which increased on reconstitution of the fibers with the phosphorylated RLC. In addition, we have shown that the level of endogenous RLC phosphorylation is a crucial determinant of the Ca2+sensitivity of force development. Studies of the effects of RLC phosphorylation on the kinetics of force activation with the caged Ca2+, DM-nitrophen, showed a slight increase in the rates of force development with low statistical significance. However, an increase from 69 to 84% of the initial steady-state force was observed when nonphosphorylated RLC-reconstituted fibers were subsequently phosphorylated with exogenous myosin light chain kinase. In conclusion, our results suggest that, although Ca2+binding to the troponin-tropomyosin complex is the primary regulator of skeletal muscle contraction, RLC play an important modulatory role in this process.

Effects ofS-nitroso-N-acetylcysteine on contractile function of reperfused skeletal muscle

1998 ◽  
Vol 274 (3) ◽  
pp. R822-R829 ◽  
Author(s):  
Long-En Chen ◽  
Anthony V. Seaber ◽  
Rima M. Nasser ◽  
Jonathan S. Stamler ◽  
James R. Urbaniak
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Control Group ◽  
Group Vi ◽  
No Donor ◽  
Early Reperfusion ◽  
Reconstructive Operations

The ultimate goal of replantation and microsurgical reconstructive operations is to regain or improve impaired function of the tissue. However, the data related to the influence of NO on tissue function are limited. This study evaluated the effects of the NO donor S-nitroso- N-acetylcysteine (SNAC) on contractile function of skeletal muscle during reperfusion. Forty-nine rats were divided into six groups. The extensor digitorum longus (EDL) muscles in groups I and II were not subjected to ischemia-reperfusion but were treated with a low (100 nmol/min) or high (1 μmol/min) dose of SNAC. In groups III- V, the EDL underwent 3 h of ischemia and 3 h of reperfusion and was also treated with low (100 nmol/min) or high doses (1 or 5 μmol/min) of SNAC. Group VI was a phosphate-buffered saline (PBS)-treated control group. Twenty additional animals were used to document systemic effects of SNAC and PBS only. SNAC or PBS was infused for 6.5 h, beginning 30 min before ischemia and continuing throughout the duration of reperfusion. Contractile testing compared the maximal twitch force, isometric tetanic contractile forces, fatigue, and fatigue half time of the experimental EDL and the contralateral nontreated EDL. The findings indicate that 1) SNAC does not influence contractile function of EDL muscle not subjected to ischemia-reperfusion, 2) SNAC significantly protects the contractile function of ischemic skeletal muscle against reperfusion injury in the early reperfusion period, and 3) the protective role of SNAC is critically dosage dependent; protection is lost at higher doses. The conclusion from this study is that supplementation with exogenous NO exerts a protective effect on the tissue against reperfusion injury.

scholarly journals Tail suspension is useful as a sarcopenia model in rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Akira Nemoto ◽  
Toru Goyagi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Experimental Model ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Whole Body ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

scholarly journals Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice

2019 ◽  
Vol 126 (1) ◽  
pp. 170-182 ◽  
Author(s):  
Hiroaki Eshima ◽  
Yoshifumi Tamura ◽  
Saori Kakehi ◽  
Kyoko Nakamura ◽  
Nagomi Kurebayashi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Contractile Function ◽  
Contractile Force ◽  
Contractile Dysfunction ◽  
Muscle Contractile ◽  
Type 2 Diabetic

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

scholarly journals Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricarda M. Haeger ◽  
Dilson E. Rassier
Keyword(s):  
Steady State ◽  
Sarcomere Length ◽  
Isometric Force ◽  
Force Production ◽  
Force Enhancement ◽  
Residual Force ◽  
Residual Force Enhancement ◽  
State Force ◽  
Isometric Forces

AbstractWhen a muscle is stretched during a contraction, the resulting steady-state force is higher than the isometric force produced at a comparable sarcomere length. This phenomenon, also referred to as residual force enhancement, cannot be readily explained by the force-sarcomere length relation. One of the most accepted mechanisms for the residual force enhancement is the development of sarcomere length non-uniformities after an active stretch. The aim of this study was to directly investigate the effect of non-uniformities on the force-producing capabilities of isolated myofibrils after they are actively stretched. We evaluated the effect of depleting a single A-band on sarcomere length non-uniformity and residual force enhancement. We observed that sarcomere length non-uniformity was effectively increased following A-band depletion. Furthermore, isometric forces decreased, while the percent residual force enhancement increased compared to intact myofibrils (5% vs. 20%). We conclude that sarcomere length non-uniformities are partially responsible for the enhanced force production after stretch.

Mitochondrial uncoupling reduces exercise capacity despite several skeletal muscle metabolic adaptations

2014 ◽  
Vol 116 (4) ◽  
pp. 364-375 ◽  
Author(s):  
A. I. Schlagowski ◽  
F. Singh ◽  
A. L. Charles ◽  
T. Gali Ramamoorthy ◽  
F. Favret ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Exercise Capacity ◽  
Maximal Exercise ◽  
Mitochondrial Fission ◽  
Critical Factor ◽  
Histochemical Staining ◽  
Running Economy ◽  
Control Group ◽  
Mitochondrial Uncoupling

The effects of mitochondrial uncoupling on skeletal muscle mitochondrial adaptation and maximal exercise capacity are unknown. In this study, rats were divided into a control group (CTL, n = 8) and a group treated with 2,4-dinitrophenol, a mitochondrial uncoupler, for 28 days (DNP, 30 mg·kg−1·day−1in drinking water, n = 8). The DNP group had a significantly lower body mass ( P < 0.05) and a higher resting oxygen uptake (V̇o2, P < 0.005). The incremental treadmill test showed that maximal running speed and running economy ( P < 0.01) were impaired but that maximal V̇o2(V̇o2max) was higher in the DNP-treated rats ( P < 0.05). In skinned gastrocnemius fibers, basal respiration (V0) was higher ( P < 0.01) in the DNP-treated animals, whereas the acceptor control ratio (ACR, Vmax/V0) was significantly lower ( P < 0.05), indicating a reduction in OXPHOS efficiency. In skeletal muscle, DNP activated the mitochondrial biogenesis pathway, as indicated by changes in the mRNA expression of PGC1-α and -β, NRF-1 and −2, and TFAM, and increased the mRNA expression of cytochrome oxidase 1 ( P < 0.01). The expression of two mitochondrial proteins (prohibitin and Ndufs 3) was higher after DNP treatment. Mitochondrial fission 1 protein (Fis-1) was increased in the DNP group ( P < 0.01), but mitofusin-1 and -2 were unchanged. Histochemical staining for NADH dehydrogenase and succinate dehydrogenase activity in the gastrocnemius muscle revealed an increase in the proportion of oxidative fibers after DNP treatment. Our study shows that mitochondrial uncoupling induces several skeletal muscle adaptations, highlighting the role of mitochondrial coupling as a critical factor for maximal exercise capacities. These results emphasize the importance of investigating the qualitative aspects of mitochondrial function in addition to the amount of mitochondria.

scholarly journals Attenuated rapid onset vasodilation with greater force production in skeletal muscle of caveolin-2−/− mice

2016 ◽  
Vol 311 (2) ◽  
pp. H415-H425 ◽  
Author(s):  
Charmain A. Fernando ◽  
Yajun Liu ◽  
Grzegorz Sowa ◽  
Steven S. Segal
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Force Production ◽  
Gluteus Maximus ◽  
Rapid Onset ◽  
Major Protein ◽  
Contraction Duration ◽  
Structural And Functional Properties ◽  
Gluteus Maximus Muscle

Caveolin-2 (Cav2) is a major protein component of caveolae in membranes of vascular smooth muscle and endothelium, yet its absence alters the ultrastructure of skeletal muscle fibers. To gain insight into Cav2 function in skeletal muscle, we tested the hypothesis that genetic deletion of Cav2 would alter microvascular reactivity and depress contractile function of skeletal muscle in vivo. In the left gluteus maximus muscle (GM) of anesthetized Cav2−/− and wild-type (WT) male mice (age, 6 mo), microvascular responses to physiological agonists and to GM contractions were studied at 34°C. For feed arteries (FA), first- (1A), second- (2A) and third-order (3A) arterioles, respective mean diameters at rest (45, 35, 25, 12 μm) and during maximal dilation (65, 55, 45, 30 μm) were similar between groups. Cumulative dilations to ACh (10−9 to 10−5 M) and constrictions to norepinephrine (10−9 to 10−5 M) were also similar between groups, as were steady-state dilations during rhythmic twitch contractions (2 and 4 Hz; 30 s). For single tetanic contractions (100 Hz; 100, 250, and 500 ms), rapid onset vasodilation (ROV) increased with contraction duration throughout networks in GM of both groups but was reduced by nearly half in Cav2−/− mice compared with WT mice ( P < 0.05). Nevertheless, maximal force during tetanic contraction was ∼40% greater in GM of Cav2−/− vs. WT mice (152 ± 14 vs. 110 ± 3 mN per square millimeter, respectively; P < 0.05). Thus, while structural and functional properties of resistance networks are well maintained in the GM of Cav2−/− mice, diminished ROV with greater force production reveals novel physiological roles for Cav2 in skeletal muscle.

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