Skeletal muscle contractile performance and ADP accumulation in adenylate kinase-deficient mice

2005 ◽  
Vol 288 (6) ◽  
pp. C1287-C1297 ◽  
Author(s):  
Chad R. Hancock ◽  
Edwin Janssen ◽  
Ronald L. Terjung
Keyword(s):  
Skeletal Muscle ◽  
Adenylate Kinase ◽  
Energy Demand ◽  
Adenine Nucleotide ◽  
Formation Rate ◽  
High Energy ◽  
Energy Demands ◽  
Whole Muscle ◽  
Muscle Contractile ◽  
Contractile Performance

The production of AMP by adenylate kinase (AK) and subsequent deamination by AMP deaminase limits ADP accumulation during conditions of high-energy demand in skeletal muscle. The goal of this study was to investigate the consequences of AK deficiency (−/−) on adenine nucleotide management and whole muscle function at high-energy demands. To do this, we examined isometric tetanic contractile performance of the gastrocnemius-plantaris-soleus (GPS) muscle group in situ in AK1−/− mice and wild-type (WT) controls over a range of contraction frequencies (30–120 tetani/min). We found that AK1−/− muscle exhibited a diminished inosine 5′-monophosphate formation rate (14% of WT) and an inordinate accumulation of ADP (∼1.5 mM) at the highest energy demands, compared with WT controls. AK-deficient muscle exhibited similar initial contractile performance (521 ± 9 and 521 ± 10 g tension in WT and AK1−/− muscle, respectively), followed by a significant slowing of relaxation kinetics at the highest energy demands relative to WT controls. This is consistent with a depressed capacity to sequester calcium in the presence of high ADP. However, the overall pattern of fatigue in AK1−/− mice was similar to WT control muscle. Our findings directly demonstrate the importance of AMP formation and subsequent deamination in limiting ADP accumulation. Whole muscle contractile performance was, however, remarkably tolerant of ADP accumulation markedly in excess of what normally occurs in skeletal muscle.

Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice

2001 ◽  
Vol 281 (3) ◽  
pp. E619-E625 ◽  
Author(s):  
M. Gorselink ◽  
M. R. Drost ◽  
W. A. Coumans ◽  
G. P. J. van Kranenburg ◽  
R. P. Hesselink ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Adenylate Kinase ◽  
Adenine Nucleotide ◽  
Recovery Period ◽  
High Energy ◽  
Wild Type ◽  
The Impact ◽  
Kinase Pathway ◽  
Contractile Performance ◽  
Atp Regeneration

Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK−/−) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK−/− mice than in wild-type animals, i.e., 23.7 ± 5.1 and 33.3 ± 6.8 mN · m · g−1 wet wt, respectively. Lower muscle ATP (20.1 ± 1.4 in CK−/− vs. 28.0 ± 2.1 μmol/g dry wt in controls) and higher IMP (1.2 ± 0.5 in CK−/− vs. 0.3 ± 0.1 μmol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK−/− mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK−/− mice and dropped to 15.5 ± 2.4 μmol/g dry wt. The significant increase in tissue IMP (2.4 ± 1.1 μmol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK−/− mice.

Metabolic and functional consequences of adenylate kinase deficiency in skeletal muscle

2005 ◽  
Author(s):  
◽  
Chad R. Hancock
Keyword(s):  
Skeletal Muscle ◽  
Adenylate Kinase ◽  
Energy State ◽  
High Energy ◽  
Metabolic Signaling ◽  
University Of Missouri ◽  
Energy Demands ◽  
Ampk Phosphorylation ◽  
Functional Consequences ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The primary function of skeletal muscle is to generate tension, and this ultimately occurs through ATP utilization. An increase in ADP and a depression in the cellular energy state are thought to be limited by the adenylate kinase (AK) reaction during high energy demands. AMP production through AK is also thought to be important for metabolic signaling, particularly during moderate energy demands. Thus, AK deficiency in muscle was evaluated during highly demanding and moderately demanding muscle contractions, using the AK1 knockout mouse (AK1-/-). The results demonstrate that AK deficiency leads to a marked elevation in free-ADP (1.5mM) at high energy demands, many fold greater than previously thought possible. These results call into question previously held views concerning the energy required for normal muscle function, because the performance was remarkably tolerant of ADP accumulation. At lower energy demands, AMPK phosphorylation was tempered in AK1-/- muscle consistent with reduced AMP production. Interestingly, other indicators of AMPK activity suggest that AMPK activation occurs normally, despite reduced AMPK phosphorylation. Thus, AK is critically important for the management of ADP during high energy demands, and may result in altered metabolic signaling at low energy demands.

Anaerobic energy provision in aged skeletal muscle during tetanic stimulation

1991 ◽  
Vol 70 (4) ◽  
pp. 1787-1795 ◽  
Author(s):  
C. B. Campbell ◽  
D. R. Marsh ◽  
L. L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Energy Demand ◽  
Energy Charge ◽  
High Energy ◽  
High Energy Phosphates ◽  
Fischer 344 ◽  
Charge Potential ◽  
Anaerobic Energy ◽  
Gastrocnemius Muscles

The effect of age on skeletal muscle anaerobic energy metabolism was investigated in adult (11 mo) and aged (25 mo) Fischer 344 rats. Hindlimb skeletal muscles innervated by the sciatic nerve were stimulated to contract with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1 Hz for 60 s, with an occluded circulation. Soleus, plantaris, and red and white gastrocnemius (WG) were sampled from control and stimulated limbs. All muscle masses were reduced with age (9-13%). Peak isometric tensions, normalized per gram of wet muscle, were lower throughout the stimulation in the aged animals (28%). The potential for anaerobic ATP provision was unaltered with age in all muscles, because resting high-energy phosphates and glycogen contents were similar to adult values. Anaerobic ATP provision during stimulation was unaltered by aging in soleus, plantaris, and red gastrocnemius muscles. In the WG, containing mainly fast glycolytic (FG) fibers, ATP and phosphocreatine contents were depleted less in aged muscle. In situ glycogenolysis and glycolysis were 90.0 +/- 4.8 and 69.3 +/- 2.6 mumol/g dry muscle (dm) in adult WG and reduced to 62.3 +/- 6.9 and 51.5 +/- 5.5 mumol/g dm, respectively, in aged WG. Consequently, total anaerobic ATP provision was lower in aged WG (224.5 +/- 20.9 mumol/g dm) vs. adult (292.6 +/- 7.6 mumol/g dm) WG muscle. In summary, the decreased tetanic tension production in aged animals was associated with a decreased anaerobic energy production in FG fibers. Reduced high-energy phosphate use and a greater energy charge potential after stimulation suggested that the energy demand was reduced in aged FG fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Towards Green and Smart Seaports: Renewable Energy and Automation Technologies for Bulk Cargo Loading Operations

2021 ◽  
Vol 25 (1) ◽  
pp. 650-665
Author(s):  
Robert Philipp ◽  
Gunnar Prause ◽  
Eunice O. Olaniyi ◽  
Florian Lemke
Keyword(s):  
Energy Demand ◽  
High Energy ◽  
Port Development ◽  
Cargo Handling ◽  
Energy Demands ◽  
Maritime Operations ◽  
Research Gap ◽  
High Share ◽  
Smart Port

Abstract In 2018, 4.1 billion tonnes of freight and 437 million passengers passed through the 1200 European ports. This dimension of geographically concentrated activities is the rationale that ports are characterised by a high-energy demand and a high share of emissions. Driven by a growing awareness for a cleaner environment, a stronger focus on sustainability and intensified environmental regulations, ports are forced to take responsibility when it comes to environmental issues. As a response, in recent studies, the concept of ‘green ports’ emerged. Simultaneously, in the context of digitalisation, the term ‘smart ports’ has received growing attention in the latest scientific discussions, too. Since an important driver towards greener maritime operations is linked to digitalisation, we argue that digital efforts in ports should next to the automation of inherent logistics processes also contribute to reducing the emissions and energy demands. Previous studies have primarily concentrated on the automation of container handling operations. Hence, there exists a research gap concerning the automation of bulk cargo handling operations in ports. Thus, this study addresses the question of how to automate the dry bulk cargo loading operations in the frame of a green and smart port development. The developed case study refers to the seaport of Wismar, whereby the results show that the digitalisation and greener port operations can be successfully aligned. Overall, this study extends the discussion on green and smart port development, while it contributes to the scientific literature by proving that both conceptual ideas can be achieved in the operating business.

scholarly journals Cardiovascular aging and the microcirculation of skeletal muscle: using contrast-enhanced ultrasound

2018 ◽  
Vol 315 (5) ◽  
pp. H1194-H1199 ◽  
Author(s):  
Emily C. Dunford ◽  
Jason S. Au ◽  
Michaela C. Devries ◽  
Stuart M. Phillips ◽  
Maureen J. MacDonald
Keyword(s):  
Skeletal Muscle ◽  
Energy Demand ◽  
High Energy ◽  
Contrast Enhanced Ultrasound ◽  
Time Intensity Curve ◽  
Noninvasive Technique ◽  
Microvascular Flow ◽  
Contrast Enhanced ◽  
Microcirculatory Function

Skeletal muscle is the largest and most important site of capillary-tissue exchange, especially during high-energy demand tasks such as exercise; however, information regarding the role of the microcirculation in maintaining skeletal muscle health is limited. Changes in microcirculatory function, as observed with aging, chronic and cardiovascular diseases, and exercise, likely precede any alterations that arise in larger vessels, although further investigation into these changes is required. One of the main barriers to addressing this knowledge gap is the lack of methodologies for quantifying microvascular function in vivo; the utilization of valid and noninvasive quantification methods would allow the dynamic evaluation of microvascular flow during periods of clinical relevance such as during increased demand for flow (exercise) or decreased demand for flow (disuse). Contrast-enhanced ultrasound (CEUS) is a promising noninvasive technique that has been used for diagnostic medicine and more recently as a complementary research modality to investigate the response of the microcirculation in insulin resistance, diabetes, and aging. To improve the reproducibility of these measurements, our laboratory has optimized the quantification protocol associated with a bolus injection of the contrast agent for research purposes. This brief report outlines the assessment of microvascular flow using the raw time-intensity curve incorporated into gamma variate response modeling. CEUS could be used to compliment any macrovascular assessments to capture a more complete picture of the aging vasculature, and the modified methods presented here provide a template for the general analysis of CEUS within a research setting.

scholarly journals Critical role for free radicals on sprint exercise-induced CaMKII and AMPKα phosphorylation in human skeletal muscle

2013 ◽  
Vol 114 (5) ◽  
pp. 566-577 ◽  
Author(s):  
David Morales-Alamo ◽  
Jesús Gustavo Ponce-González ◽  
Amelia Guadalupe-Grau ◽  
Lorena Rodríguez-García ◽  
Alfredo Santana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Demand ◽  
Human Skeletal Muscle ◽  
Critical Role ◽  
Recovery Period ◽  
Muscle Metabolism ◽  
High Energy ◽  
Vastus Lateralis Muscle ◽  
Sprint Exercise

The extremely high energy demand elicited by sprint exercise is satisfied by an increase in O2 consumption combined with a high glycolytic rate, leading to a marked lactate accumulation, increased AMP-to-ATP ratio, and reduced NAD+/NADH.H+ and muscle pH, which are accompanied by marked Thr172 AMP-activated protein kinase (AMPK)-α phosphorylation during the recovery period by a mechanism not fully understood. To determine the role played by reactive nitrogen and oxygen species (RNOS) on Thr172-AMPKα phosphorylation in response to cycling sprint exercise, nine voluntary participants performed a single 30-s sprint (Wingate test) on two occasions: one 2 h after the ingestion of placebo and another after the intake of antioxidants (α-lipoic acid, vitamin C, and vitamin E) in a double-blind design. Vastus lateralis muscle biopsies were obtained before, immediately postsprint, and 30 and 120 min postsprint. Performance and muscle metabolism were similar during both sprints. The NAD+-to-NADH.H+ ratio was similarly reduced (84%) and the AMP-to-ATP ratio was similarly increased (×21-fold) immediately after the sprints. Thr286 Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Thr172-AMPKα phosphorylations were increased after the control sprint (with placebo) but not when the sprints were preceded by the ingestion of antioxidants. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known inhibitory mechanism of Thr172-AMPKα phosphorylation, was increased only with antioxidant ingestion. In conclusion, RNOS play a crucial role in AMPK-mediated signaling after sprint exercise in human skeletal muscle. Antioxidant ingestion 2 h before sprint exercise abrogates the Thr172-AMPKα phosphorylation response observed after the ingestion of placebo by reducing CaMKII and increasing Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation. Sprint performance, muscle metabolism, and AMP-to-ATP and NAD+-to-NADH.H+ ratios are not affected by the acute ingestion of antioxidants.

Metabolic control over the oxygen consumption flux in intact skeletal muscle: in silico studies

2006 ◽  
Vol 291 (6) ◽  
pp. C1213-C1224 ◽  
Author(s):  
Piotr Liguzinski ◽  
Bernard Korzeniewski
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Metabolic Control ◽  
In Silico ◽  
High Energy ◽  
Activation Mechanism ◽  
Atp Production ◽  
Atp Turnover ◽  
Energy Demands

It has been postulated previously that a direct activation of all oxidative phosphorylation complexes in parallel with the activation of ATP usage and substrate dehydrogenation (the so-called each-step activation) is the main mechanism responsible for adjusting the rate of ATP production by mitochondria to the current energy demand during rest-to-work transition in intact skeletal muscle in vivo. The present in silico study, using a computer model of oxidative phosphorylation developed previously, analyzes the impact of the each-step-activation mechanism on the distribution of control (defined within Metabolic Control Analysis) over the oxygen consumption flux among the components of the bioenergetic system in intact oxidative skeletal muscle at different energy demands. It is demonstrated that in the absence of each-step activation, the oxidative phosphorylation complexes take over from ATP usage most of the control over the respiration rate and oxidative ATP production at higher (but still physiological) energy demands. This leads to a saturation of oxidative phosphorylation, impossibility of a further acceleration of oxidative ATP synthesis, and dramatic drop in the phosphorylation potential. On the other hand, the each-step-activation mechanism allows maintenance of a high degree of the control exerted by ATP usage over the ATP turnover and oxygen consumption flux even at high energy demands and thus enables a potentially very large increase in ATP turnover. It is also shown that low oxygen concentration shifts the metabolic control from ATP usage to cytochrome oxidase and thus limits the oxidative ATP production.

scholarly journals A 31P-n.m.r. study of the acute effects of β-blockade on the bioenergetics of skeletal muscle during contraction

1987 ◽  
Vol 246 (1) ◽  
pp. 163-172 ◽  
Author(s):  
R A Challiss ◽  
D J Hayes ◽  
G K Radda
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
High Energy ◽  
Muscle Stimulation ◽  
Stimulation Protocol ◽  
Unilateral Stimulation ◽  
Short Period ◽  
Supramaximal Stimulation ◽  
Contractile Performance ◽  
Stimulation Of

1. The effects of beta-adrenoceptor antagonist administration on skeletal muscle contractile performance and bioenergetics in vivo have been investigated during unilateral sciatic nerve stimulation in the rat. 2. Two muscle stimulation protocols have been used: supramaximal stimulation at 4 Hz, or incremental supramaximal stimulation at 1, 2 and 4 Hz. Changes in high-energy phosphate concentrations were followed using 31P-n.m.r., and gastrocnemius muscle twitch characteristics were monitored continuously. 3. Under all conditions investigated, DL-propranolol administration (2.5 mg/kg body wt.) caused a significant decrease in cyclic AMP concentrations in resting and stimulated gastrocnemius muscle, prevented an increase in heart rate upon muscle stimulation, but did not affect plasma glucose, fatty acid or lactate concentrations in comparison with values obtained in control experiments. 4. Administration of DL-propranolol 5 min or 35 min before unilateral stimulation of 4 Hz had no effect on changes in muscle phosphocreatine, ATP or Pi concentrations, intracellular pH or contractile performance. 5. In contrast, animals receiving DL-propranolol 5 min before unilateral stimulation of 1, 2 and 4 Hz showed a significant deterioration in gastrocnemius muscle tension development during 2 and 4 Hz stimulation compared with control animals. Concurrent with this change in contractile performance was a higher muscle concentration of phosphocreatine, a lower concentration of Pi and no significant change in intramuscular pH compared with control experiments. 6. The changes in muscle performance and bioenergetics observed during the incremental stimulation protocol were not observed when D-propranolol was administered and could be completely circumvented by a short period of muscle stimulation of 4 Hz prior to initiation of the incremental stimulation protocol. 7. Mechanisms are discussed which may account for the failure of gastrocnemius muscle to generate the expected force during the incremental stimulation protocol in the presence of beta-blockade.

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