Phosphagen and intracellular pH changes during contraction of creatine-depleted rat muscle

1986 ◽  
Vol 250 (2) ◽  
pp. C264-C274 ◽  
Author(s):  
R. A. Meyer ◽  
T. R. Brown ◽  
B. L. Krilowicz ◽  
M. J. Kushmerick
Keyword(s):  
Steady State ◽  
Intracellular Ph ◽  
Muscle Metabolism ◽  
Surface Coil ◽  
The Difference ◽  
Transfer Method ◽  
Fast Twitch ◽  
Resting Muscle

To evaluate the functional role of phosphocreatine (PCr) and creatine in muscle metabolism, these compounds were depleted by feeding rats the creatine analogue, beta-guanidinopropionate (beta-GPA, 2% of diet). Changes in phosphate metabolites and intracellular pH were monitored in gastrocnemius muscle in situ by phosphorus nuclear magnetic resonance (31P-NMR) at 162 MHz using the surface coil technique. After 3 mo of feeding, 25 mumol/g of phosphorylated beta-GPA (beta-GPAP) had accumulated, and PCr, creatine, and ATP levels were reduced to 6, 17, and 56%, respectively, compared with muscles of control animals. In resting muscle, there was no measurable exchange of phosphate between beta-GPAP and ATP by the NMR saturation transfer method. During muscle stimulation at 1 and 5 Hz, the maximum net rate of beta-GPAP hydrolysis was 10% that of PCr in control muscles, so that after 150 s inorganic phosphate had increased to less than 50% of the level attained in control muscles. At both rates, peak twitch force declined toward a steady state more rapidly in beta-GPA-loaded muscles, but after 100 s force was either not different (1 Hz) or significantly greater (5 Hz) in the beta-GPA-fed animals. Intracellular pH initially decreased more rapidly during stimulation and recovered more rapidly afterward in the beta-GPA-loaded muscles compared with controls. This difference could be explained by the difference in expected proton consumption due to net PCr hydrolysis. However, despite buffering by PCr hydrolysis, pH ultimately decreased more in control muscle (6.1 vs. 6.3 for 5 Hz), indicating greater acid accumulation compared with beta-GPA-loaded muscles. In the superficial, predominantly fast-twitch glycolytic section of muscles clamp-frozen after 5-Hz stimulation for 150 s, lactate accumulation was twofold greater in controls. The results indicate that PCr is not essential for steady-state energy production but that the phosphate from PCr hydrolysis may be important for maximum activation of glycogenolysis and/or glycolysis.

Static Pressure-Volume Curves for the Lung of the Frog (Rana Pipiens)

1978 ◽  
Vol 76 (1) ◽  
pp. 149-165 ◽  
Author(s):  
G. M. HUGHES ◽  
G. A. VERGARA
Keyword(s):  
Volume Change ◽  
Rana Pipiens ◽  
Static Pressure ◽  
Large Diameter ◽  
The Difference ◽  
Isolated Lungs ◽  
Precise Role ◽  
Different Parts

1. Static pressure/volume curves have been determined for isolated frog lungs inflated with either air or saline. In both cases a hysteresis was present: the pressure required to produce unit change of volume being greater during inflation than deflation. 2. The pressure necessary for a given volume change was less for the saline-filled than the air-filled lungs. The difference between these curves is due to the surface tension at the air/lung interface. 3. Pressure/volume curves for air-filled lungs in situ were similar to curves for isolated lungs. However, a greater pressure was required for the same volume change during both inflation and deflation. 4. Compliance was calculated from different parts of air pressure/volume curves and gave values greater than those obtained using similar calculations for higher vertebrates. 5. These observations support other evidence for the presence of a surfactant in the lung lining of frogs in spite of the relatively large diameter of their ‘alveoli.’ The precise role of such a lining is uncertain and it is concluded that similar forces may be involved during the inflation and deflation of lungs of frogs and higher vertebrates in spite of differences in gross morphology.

scholarly journals Role of convective O2 delivery in determiningV˙o 2 on-kinetics in canine muscle contracting at peak V˙o 2

2000 ◽  
Vol 89 (4) ◽  
pp. 1293-1301 ◽  
Author(s):  
Bruno Grassi ◽  
Michael C. Hogan ◽  
Kevin M. Kelley ◽  
William G. Aschenbach ◽  
Jason J. Hamann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Muscle Fatigue ◽  
Oxidative Metabolism ◽  
Muscle Blood Flow ◽  
Content Difference ◽  
O2 Delivery ◽  
Gastrocnemius Muscles

A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl Physiol 85: 1394–1403, 1998) showed that convective O2 delivery to muscle did not limit O2 uptake (V˙o 2) on-kinetics during transitions from rest to contractions at ∼60% of peakV˙o 2. The present study aimed to determine whether this finding is also true for transitions involving contractions of higher metabolic intensities.V˙o 2 on-kinetics were determined in isolated canine gastrocnemius muscles in situ ( n = 5) during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions corresponding to the muscle peakV˙o 2. Two conditions were compared: 1) spontaneous adjustment of muscle blood flow (Q˙) (Control) and 2) pump-perfused Q˙, adjusted ∼15–30 s before contractions at a constant level corresponding to the steady-state value during contractions in Control (Fast O2 Delivery). In Fast O2 Delivery, adenosine was infused intra-arterially. Q˙ was measured continuously in the popliteal vein; arterial and popliteal venous O2 contents were measured at rest and at 5- to 7-s intervals during the transition. Muscle V˙o 2 was determined as Q˙times the arteriovenous blood O2 content difference. The time to reach 63% of the V˙o 2 difference between resting baseline and steady-state values during contractions was 24.9 ± 1.6 (SE) s in Control and 18.5 ± 1.8 s in Fast O2 Delivery ( P < 0.05). FasterV˙o 2 on-kinetics in Fast O2Delivery was associated with an ∼30% reduction in the calculated O2 deficit and with less muscle fatigue. During transitions involving contractions at peak V˙o 2, convective O2 delivery to muscle, together with an inertia of oxidative metabolism, contributes in determining theV˙o 2 on-kinetics.

scholarly journals Age-Related Alterations in Immune Contexture Are Associated with Aggressiveness in Rhabdomyosarcoma

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1380 ◽  
Author(s):  
Patrizia Gasparini ◽  
Orazio Fortunato ◽  
Loris De Cecco ◽  
Michela Casanova ◽  
Maria Federica Iannó ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Tumor Biology ◽  
Muscle Metabolism ◽  
Γδ T Cells ◽  
Resting Cells ◽  
Over Expression ◽  
Age Related ◽  
Immune Contexture

Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and access to care remain a challenge and whose survival lacks behind that of children diagnosed with histologically similar tumors. Understanding the tumor biology that differentiates children from AYA-RMS could provide critical information and drive new initiatives to improve the final outcome. MicroRNA (miRNA) and gene expression profiling (GEP) was evaluated in a RMS cohort of 49 tumor and 15 non-neoplastic tissues. miRNAs analysis identified miR-223 over-expression and miR-431 down-regulation in AYA, validated by Real-Time PCR and miRNA in situ hybridization (ISH). GEP analysis detected 793 age-correlated genes in tumors, of which 194 were anti-correlated. NOTCH2, FGFR1/2 were significantly down-modulated in AYA-RMS. miR-223 was associated with up-regulation of epithelial mesenchymal translation (EMT) and inflammatory pathways, whereas miR-431 was correlated to myogenic differentiation and muscle metabolism. GEP showed an increase in genes associated with CD4 memory resting cells and a decrease in genes associated with γδ T-cells in AYA-RMS. Immunohistochemistry (IHC) analysis demonstrated an increase of infiltrated CD4, CD8, and neutrophils in AYA-RMS tumors. Our results show that aggressiveness of AYA-RMS could be explained by differences in microenvironmental signal modulation mediated by tumor cells, suggesting a fundamental role of immune contexture in AYA-RMS development.

THE ROLE OF PANIC IN THE ROOM EVACUATION PROCESS

2006 ◽  
Vol 17 (03) ◽  
pp. 419-434 ◽  
Author(s):  
DANIEL R. PARISI ◽  
CLAUDIO O. DORSO
Keyword(s):  
Steady State ◽  
Strong Correlation ◽  
Point Of View ◽  
Force Model ◽  
Social Force ◽  
Call Blocking ◽  
Social Force Model ◽  
The Social ◽  
The Difference

In the present work we studied the room evacuation problem using the social force model introduced by Helbing and coworkers. The "faster is slower" effect induced by panic was analyzed. It could be explained in terms of increasing mean clogging delays which shows a strong correlation with certain structures that we call "blocking clusters". Also a steady state version of the problem was implemented. It shows that, from a macroscopic point of view, the optimal evacuation efficiency correspond to the state at which the difference between the system desire force minus the system granular force is maximum.

scholarly journals Faster adjustment of O2delivery does not affect V˙o 2 on-kinetics in isolated in situ canine muscle

1998 ◽  
Vol 85 (4) ◽  
pp. 1394-1403 ◽  
Author(s):  
Bruno Grassi ◽  
L. Bruce Gladden ◽  
Michele Samaja ◽  
Creed M. Stary ◽  
Michael C. Hogan
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Experimental Model ◽  
Oxidative Metabolism ◽  
Constant Level ◽  
Model Elimination ◽  
Content Difference ◽  
The Difference ◽  
Gastrocnemius Muscles

The mechanism(s) limiting muscle O2 uptake (V˙o 2) kinetics was investigated in isolated canine gastrocnemius muscles ( n = 7) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60–70% of peakV˙o 2). Two conditions were mainly compared: 1) spontaneous adjustment of blood flow (Q˙) [control, spontaneousQ˙ (C Spont)]; and 2) pump-perfusedQ˙, adjusted ∼15 s before contractions at a constant level corresponding to the steady-state value during contractions in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2 Delivery, 1–2 ml/min of 10−2 M adenosine were infused intra-arterially to prevent inordinate pressure increases with the elevated Q˙. The purpose of the study was to determine whether a faster adjustment of O2 delivery would affectV˙o 2 kinetics.Q˙ was measured continuously; arterial ([Formula: see text]) and popliteal venous ([Formula: see text]) O2 contents were determined at rest and at 5- to 7-s intervals during contractions; O2 delivery was calculated asQ˙ ⋅ [Formula: see text], and V˙o 2 was calculated asQ˙ ⋅ arteriovenous O2 content difference. Times to reach 63% of the difference between baseline and steady-stateV˙o 2 during contractions were 23.8 ± 2.0 (SE) s in C Spont and 21.8 ± 0.9 s in Fast O2 Delivery (not significant). In the present experimental model, elimination of any delay in O2 delivery during the rest-to-contraction transition did not affect muscleV˙o 2 kinetics, which suggests that this kinetics was mainly set by an intrinsic inertia of oxidative metabolism.

On the role of phonology and discourse in Francilian Frenchwh-questions

2010 ◽  
Vol 47 (1) ◽  
pp. 129-162 ◽  
Author(s):  
FATIMA HAMLAOUI
Keyword(s):  
Recent Work ◽  
Metropolitan Area ◽  
Theoretic Analysis ◽  
Discourse Context ◽  
The Difference ◽  
The Right ◽  
Sentence Stress

It is argued that in Francilian French, the dialect of French spoken in the Paris metropolitan area, in-situ and frontedwh-questions have the same answerhood conditions but vary with respect to their respective focus-set (Reinhart 2006). The difference between the two types of questions lies in the discourse status of their non-whportion. Whereas thewh-phrase is never discourse-given, the non-whportion may or may not be, depending on the discourse context. In Francilian French in-situwh-questions, the non-whportion must be discourse-given. As this language exhibits a strong requirement on sentence stress to be kept rightmost it cannot, in contrast with English, assign sentence stress to a frontedwh-phrase when the non-whportion is discourse-given and needs to be destressed. The only way to simultaneously destress discourse-given items and keep sentence stress rightmost is by aligning thewh-phrase with the right edge of the clause. Whereas in Hungarian prosody triggers movement (Szendrői 2003), in Francilian French, prosody prevents it from occurring. An Optimal Theoretic analysis in the spirit of much recent work on focus and givenness in declaratives (Samek-Lodovici 2005, Féry & Samek-Lodovici 2006) captures this phenomenon.

scholarly journals Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

1995 ◽  
Vol 105 (2) ◽  
pp. 177-208 ◽  
Author(s):  
J H Ravesloot ◽  
T Eisen ◽  
R Baron ◽  
W F Boron
Keyword(s):  
Intracellular Ph ◽  
Imaging System ◽  
Ph Regulation ◽  
Neonatal Rat ◽  
Hill Coefficient ◽  
Acid Base ◽  
Buffering Power ◽  
Acid Extrusion

Osteoclasts resorb bone by pumping of H+ into a compartment between the cell and the bone surface. Intracellular pH (pHi) homeostasis requires that this acid extrusion, mediated by a vacuolar-type H+ ATPase, be complemented by other acid-base transporters. We investigated acid-extrusion mechanisms of single, freshly isolated, neonatal rat osteoclasts. Cells adherent to glass coverslips were studied in the nominal absence of CO2/HCO3-, using the pH-sensitive dye BCECF and a digital imaging system. Initial pHi averaged 7.31 and was uniform throughout individual cells. Intrinsic buffering power (beta 1) decreased curvilinearly from approximately 25 mM at pHi = 6.4 to approximately 6.0 mM at pHi = 7.4. In all polygonally shaped osteoclasts, and approximately 60% of round osteoclasts (approximately 20% of total), pHi recovery from acid loads was mediated exclusively by Na-H exchange. In these pattern-1 cells, pHi recovery was 95% complete within 200 s, and was blocked by removing Na+, or by applying 1 mM amiloride, 50 microM ethylisopropylamiloride (EIPA), or 50 microM hexamethyleneamiloride (HMA). The apparent K1/2 for HMA ([Na+]o = 150 mM) was 49 nM, and the apparent K1/2 for Na+ was 45 mM. Na-H exchange, corrected for amiloride-insensitive fluxes, was half maximal at pHi 6.73, with an apparent Hill coefficient for intracellular H+ of 2.9. Maximal Na-H exchange averaged 741 microM/s. In the remaining approximately 40% of round osteoclasts (pattern-2 cells), pHi recovery from acid loads was brisk even in the absence of Na+ or presence of amiloride. This Na(+)-independent pHi recovery was blocked by 7-chloro-4-nitrobenz-2-oxa-1,3-diazol (NBD-Cl), a vacuolar-type H+ pump inhibitor. Corrected for NBD-Cl insensitive fluxes, H+ pump fluxes decreased approximately linearly from 96 at pHi 6.8 to 11 microM/s at pHi 7.45. In approximately 45% of pattern-2 cells, Na+ readdition elicited a further pHi recovery, suggesting that H+ pumps and Na-H exchangers can exist simultaneously. We conclude that, under the conditions of our study, most neonatal rat osteoclasts express Na-H exchangers that are probably of the ubiquitous basolateral subtype. Some cells express vacuolar-type H+ pumps in their plasma membrane, as do active osteoclasts in situ.

Peripheral O2 diffusion does not affect V˙o 2 on-kinetics in isolated in situ canine muscle

1998 ◽  
Vol 85 (4) ◽  
pp. 1404-1412 ◽  
Author(s):  
Bruno Grassi ◽  
L. Bruce Gladden ◽  
Creed M. Stary ◽  
Peter D. Wagner ◽  
Michael C. Hogan
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Elevated Blood ◽  
Dissociation Curve ◽  
Content Difference ◽  
Difference Formula ◽  
O2 Diffusion ◽  
The Difference ◽  
Gastrocnemius Muscles

To test the hypothesis that muscle O2 uptake (V˙o 2) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined theV˙o 2 on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles ( n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60–70% peakV˙o 2). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q˙), at a level measured at steady state during contractions in preliminary trials with spontaneous Q˙. Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q˙. Q˙ was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, andV˙o 2 was calculated asQ˙ ⋅ arteriovenous O2 content difference.[Formula: see text] at 50% Hbo 2saturation (P50) was calculated. Mean capillary [Formula: see text](P [Formula: see text]) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,P [Formula: see text]was higher in Hyperoxia (97 ± 9 Torr) vs. Control (53 ± 3 Torr) and in Hyperoxia+RSR-13 (197 ± 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-stateV˙o 2 during contractions was 24.7 ± 2.7 s in Control, 26.3 ± 0.8 s in Hyperoxia, and 24.7 ± 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increasedP [Formula: see text]at constant O2 delivery) during the rest-to-contraction (60–70% of peakV˙o 2) transition did not affect muscle V˙o 2on-kinetics.

AMP deaminase binding in contracting rat skeletal muscle

1992 ◽  
Vol 263 (2) ◽  
pp. C287-C293 ◽  
Author(s):  
K. W. Rundell ◽  
P. C. Tullson ◽  
R. L. Terjung
Keyword(s):  
Skeletal Muscle ◽  
Iodoacetic Acid ◽  
Amp Deaminase ◽  
Energy Demands ◽  
Slow Twitch Muscle ◽  
Fast Twitch ◽  
Resting Muscle

AMP deaminase, which hydrolyses AMP to inosine 5'-monophosphate (IMP) and NH3 at high rates during excessive energy demands in skeletal muscle, is activated when bound to myosin in vitro. We evaluated AMP deaminase binding in vivo during muscle contractions to assess whether binding 1) is inherent to deamination and found only with high rates of IMP production or simply coincident with the contractile process and 2) requires cellular acidosis. AMP deaminase activity (mumol.min-1.g-1) was measured in the supernatant (free) and 10(4)-g pellet (bound) homogenate fractions of muscle of anesthetized rats after in situ contractions to determine the percent bound. In resting muscle, nearly all (approximately 90%) AMP deaminase is free (cytosolic). During contractions when energy balance was well maintained, binding did not significantly differ from resting values. However, during intense contraction conditions that lead to increased IMP concentration, binding increased to approximately 60% (P less than 0.001) in fast-twitch and approximately 50% in slow-twitch muscle. Binding increased in an apparent first-order manner and preceded initiation of IMP formation. Further, binding rapidly declined within 1 min after cessation of intense stimulation, even though the cell remained extremely acidotic. Extensive binding during contractions was also evident without cellular acidosis (iodoacetic acid-treated muscle). Thus the in vivo AMP deaminase-myosin complex association/dissociation is not coupled to changes in cellular acidosis. Interestingly, binding remained elevated after contractions, if energy recovery was limited by ischemia. Our results are consistent with myosin binding having a role in AMP deaminase activation and subsequent IMP formation in contracting muscle.

Effect of contractile activity on protein turnover in skeletal muscle mitochondrial subfractions

2000 ◽  
Vol 88 (5) ◽  
pp. 1601-1606 ◽  
Author(s):  
Michael K. Connor ◽  
Olga Bezborodova ◽  
C. Patricia Escobar ◽  
David A. Hood
Keyword(s):  
Mitochondrial Biogenesis ◽  
Protein Turnover ◽  
Gastrocnemius Muscle ◽  
Contractile Activity ◽  
Recovery Period ◽  
Chronic Stimulation ◽  
Fast Twitch ◽  
Isolated Rat

To determine the role of intramitochondrial protein synthesis (PS) and degradation (PD) in contractile activity-induced mitochondrial biogenesis, we evaluated rates of [35S]methionine incorporation into protein in isolated rat muscle subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. Rates of PS ranged from 47 to 125% greater ( P < 0.05) in IMF compared with SS mitochondria. Intense, acute in situ contractile activity (10 Hz, 5 min) of fast-twitch gastrocnemius muscle resulted in a 50% decrease in PS ( P < 0.05) in SS but not IMF mitochondria. Recovery, or continued contractile activity (55 min), reestablished PS in SS mitochondria. In contrast, PS was not affected in either SS or IMF mitochondria after prolonged (60-min) contractile activity in the presence or absence of a recovery period. PD was not influenced by 5 min of contractile activity in the presence or absence of recovery but was reduced after 60 min of contractions followed by recovery. Chronic stimulation (10 Hz, 3 h/day, 14 days) increased muscle cytochrome- c oxidase activity by 2.2-fold but reduced PS in IMF mitochondria by 29% ( P < 0.05; n = 4). PS in SS mitochondria and PD in both subfractions were not changed by chronic stimulation. Thus acute contractile activity exerts differential effects on protein turnover in IMF and SS mitochondria, and it appears that intramitochondrial PS does not limit the extent of chronic contractile activity-induced mitochondrial biogenesis.

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