21 results on '"Ventura-Clapier R"'
Search Results
2. Recovery of contractile and metabolic phenotypes in regenerating slow muscle after notexin-induced or crush injury
- Author
-
Fink, E., Fortin, D., Serrurier, B., Ventura-Clapier, R., and Bigard, A.X.
- Abstract
The recovery of metabolic pathways after muscle damage has been poorly studied. We investigated the myosin heavy chain (MHC) isoform transitions and the recovery of citrate synthase (CS) activity, isoform distribution of lactate dehydrogenase (LDH) and creatine kinase (CK) in slow muscles after two types of injury. Muscle degeneration was induced in left soleus muscles of male Wistar rats by either notexin injection or crushing and the regenerative process was examined from 2 to 56 days after injury. Myosin transition occurred earlier after notexin than after crush injury. Fast-type IIx and more particularly type IIa MHC isoform disappeared by day 28 after notexin inoculation, while they were still detected long after in crushed muscles. A full recovery of both the CS activity and the specific activity of the H-LDH subunit was observed from day 42 in notexin-treated muscles, while values measured in crushed muscles remained significantly lower than in non-injured muscles (P> 0.05). The activity of the mitochondrial isoform of CK (mi-CK) was markedly affected by the type of injury (P> 0.001), and failed to reach normal levels after crush injury (P> 0.05). The results of this study show that the relatively rapid MHC transitions during regeneration contrasts with the slow recovery in the oxidative capacity. The recovery of the oxidative capacity remained incomplete after crush injury, a model of injury known to lead to disruption of the basal lamina and severe interruption of the vascular and nerve supply.
- Published
- 2003
- Full Text
- View/download PDF
3. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles
- Author
-
Garnier, A., Fortin, D., Deloménie, C., Momken, I., Veksler, V., and Ventura‐Clapier, R.
- Abstract
Congestive heart failure (CHF) induces alterations in energy metabolism and mitochondrial function that span cardiac as well as skeletal muscles. Whether these defects originate from altered mitochondrial DNA copy number and/or mitochondrial gene transcription is not known at present, nor are the factors that control mitochondrial capacity in different muscle types completely understood. We used an experimental model of CHF induced by aortic banding in the rat and investigated mitochondrial respiration and enzyme activity of biochemical mitochondrial markers in cardiac, slow and fast skeletal muscles. We quantified mitochondrial DNA (mtDNA), expression of nuclear (COX IV) and mitochondrial (COX I) encoded cytochrome coxidase subunits as well as nuclear factors involved in mitochondrial biogenesis and in the necessary coordinated interplay between nuclear and mitochondrial genomes in health and CHF. CHF induced a decrease in oxidative capacity and mitochondrial enzyme activities with a parallel decrease in the mRNA level of COX I and IV, but no change in mtDNA content. The expression of the peroxisome proliferator activated receptor gamma co‐activator 1α (PGC‐1α) gene was downregulated in CHF, as well as nuclear respiratory factor 2 and mitochondrial transcription factor A, which act downstream from PGC‐1α. Most interestingly, only the level of PGC‐1α expression was strongly correlated with muscle oxidative capacity in cardiac and skeletal muscles, both in healthy and CHF rats. Mitochondrial gene transcription is reduced in CHF, and PGC‐1α appears as a potential modulator of muscle oxidative capacity under these experimental conditions.
- Published
- 2003
- Full Text
- View/download PDF
4. Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle
- Author
-
Zoll, J., Sanchez, H., N'Guessan, B., Ribera, F., Lampert, E., Bigard, X., Serrurier, B., Fortin, D., Geny, B., Veksler, V., Ventura‐Clapier, R., and Mettauer, B.
- Abstract
This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak V̇O2, expressed in ml min−1kg−1). All volunteers underwent a cyclo‐ergometric incremental exercise test to estimate their peak V̇O2and V̇O2at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (V̇0) or in the presence (V̇max) of saturating [ADP]. While V̇0was similar, V̇maxdiffered among groups (sedentary, 3.7 ± 0.3, active, 5.9 ± 0.9 and athletic, 7.9 ± 0.5 μmol O2min−1(g dry weight)−1). V̇maxwas correlated with peak V̇O2(P< 0.01, r= 0.63) and with V̇T(P< 0.01, r= 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (V̇max/V̇0) in the athletic individuals. The mitochondrial Kmfor ADP was significantly higher in athletic subjects (P< 0.01). Mitochondrial CK (mi‐CK) activation by addition of creatine induced a marked decrease in Kmin athletic individuals only, indicative of an efficient coupling of mi‐CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co‐ordination of energy fluxes by CK for higher efficacy.
- Published
- 2002
- Full Text
- View/download PDF
5. Effect of cyclosporin A and its vehicle on cardiac and skeletal muscle mitochondria: relationship to efficacy of the respiratory chain
- Author
-
Sanchez, H, Zoll, J, Bigard, X, Veksler, V, Mettauer, B, Lampert, E, Lonsdorfer, J, and Ventura‐Clapier, R
- Abstract
Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues.We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (Vmax) of cardiac, soleus and gastrocnemius muscles of rats by an oxygraphic method in saponin skinned muscle fibres. The effects of Sandimmun (a formulation of CsA), vehicle of Sandimmun (cremophor and ethanol (EtOH)), CsA in EtOH and EtOH alone were tested. Increasing concentrations (5 – 20 – 50 – 100 μM) of CsA (or vehicles) were used.Sandimmun profoundly altered the Vmaxof all muscles. For example, at 20 μM, inhibition reached 18±3, 23±5, 45±5%, for heart, soleus and gastrocnemius respectively. There were only minor effects of CsA diluted in EtOH and EtOH alone on Vmaxof cardiac muscle. Because the effects of vehicle on Vmaxwere similar or higher than those of Sandimmun, the inhibition of oxidative capacity could be entirely attributed to the vehicle for all muscles.Next, we investigated the potential sites of action of the vehicle on the different complexes of the mitochondrial respiratory chain by using specific substrates and inhibitors. The vehicle affected mitochondrial respiration mainly at the level of complex I (∼−85% in skeletal muscles, and −32% in heart), but also at complex IV (∼−26% for all muscles).The mechanism of action of the vehicle on the mitochondrial membrane and the implications for the clinical use of immunosuppressive drugs are discussed.
- Published
- 2001
- Full Text
- View/download PDF
6. Dual Influence of Disease and Increased Load on Diaphragm Muscle in Heart Failure
- Author
-
De Sousa, E, Veksler, V, Bigard, X, Mateo, P, Serrurier, B, and Ventura-Clapier, R
- Abstract
We have recently shown that mitochondrial function and energy metabolism are altered in the myocardium as well as in slow and fast locomotor muscles of rats subjected to prolonged congestive heart failure (CHF) suggesting a generalized metabolic myopathy in heart failure. Here, we investigate whether the diaphragm of CHF animals, which experiences both increased work and the general systemic influence of heart failure, will also be susceptible to altered energy metabolism. Biopsies were obtained from the costal diaphragm of failing rats 8 months after aortic banding. A marked increase in type I and type IIa myosin heavy chains at the expense of types IIx and IIb, suggests an adaptation towards a slower phenotype. Glycolytic enzymes decreased in CHF diaphragm with an increase in the H:M lactate dehydrogenase isoenzyme ratio. These results suggest a reorientation of the diaphragm muscle towards a slow, fatigue-resistant phenotype. However, maximal oxidative capacity assessed in saponin-permeabilized fibers in the presence of ADP was considerably reduced in CHF diaphragm (7.7±0.4 v11.8±0.7 μmol O2/min/g dry weight in sham P<0.001), suggesting an alteration in oxidative phosphorylation. Furthermore, ADP sensitivity of CHF mitochondria was significantly increased (apparentKmfor ADP 308±21 v945±106 μMin sham P<0.001), whereas sensitivity to ADP in the presence of creatine was comparable (Km79±12 v90±11μMin sham). In heart failure, therefore, the diaphragm muscle seems to adapt towards a more slow and economical contraction as a result of increased workload, but this adaptation is limited by the disease-induced altered mitochondrial function.
- Published
- 2001
- Full Text
- View/download PDF
7. Response of mitochondrial function to hypothyroidism in normal and regenerated rat skeletal muscle
- Author
-
Zoll, J., Ventura-Clapier, R., Serrurier, B., and Bigard, A.
- Abstract
Although thyroid hormones induce a well known decrease in muscle oxidative capacity, nothing is known concerning their effects on mitochondrial function and regulation in situ. Similarly, the influence of regeneration process is not completely understood. We investigated the effects of hypothyroidism on mitochondrial function in fast gastrocnemius (GS) and slow soleus (SOL) muscles either intact or having undergone a cycle of degeneration/regeneration (Rg SOL) following a local injection of myotoxin. Thyroid hormone deficiency was induced by thyroidectomy and propylthiouracyl via drinking water. Respiration was measured in muscle fibres permeabilised by saponin in order to assess the oxidative capacity of the muscles and the regulation of mitochondria in situ. Oxidative capacities were 8.9 in SOL, 8.5 in Rg SOL and 5.9 μmol O2/min/g dry weight in GS and decreased by 52, 42 and 39% respectively (P< 0.001) in hypothyroid rats. Moreover, the Kmof mitochondrial respiration for the phosphate acceptor ADP exhibited a two-fold decrease in Rg SOL and intact SOL by hypothyroidism (P< 0.01), while mitochondrial creatine kinase activity and sensitivity of mitochondrial respiration to creatine were not altered. The results of this study demonstrate that hypothyroidism markedly altered the sensitivity of mitochondrial respiration to ADP but not to creatine in SOL muscles, suggesting that mitochondrial regulation could be partially controlled by thyroid hormones. On the other hand, mitochondrial function completely recovered following regeneration/degeneration, suggesting that thyroid hormones are not involved in the regeneration process per se.
- Published
- 2001
- Full Text
- View/download PDF
8. Lack of coordinated changes in metabolic enzymes and myosin heavy chain isoforms in regenerated muscles of trained rats
- Author
-
Bigard, A., Mateo, Ph., Sanchez, H., Serrurier, B., and Ventura-Clapier, R.
- Abstract
We investigated training-induced changes in biochemical properties and myosin heavy chain (MHC) composition of regenerated (cardiotoxin-injected) plantaris muscles (PLA) in rats either maintained sedentary (S, n= 9) or endurance trained on a treadmill over a 8-week period (T, n= 7). Both endurance training and regeneration altered the pattern of fast MHC expression. An analysis of the two-way interaction between training and regeneration showed that the relative content of type IIa MHC was affected (P< 0.05). The 140% increase in type IIa MHC observed in regenerated PLA from T rats compared with nontreated muscle of S rats, exceeded the 102% increase resulting from the combination of regeneration alone (26%) and training alone (61%). A similar interaction between training and regeneration was shown for the percentage of fibres expressing either type IIa or type IIb MHC (P< 0.05). In contrast, a significant increase in the citrate synthase (CS) activity was shown in PLA as a result of endurance training, without specific effect of regeneration. Furthermore, training-induced changes in CK and LDH isoenzyme distribution occurred to a similar extent in regenerated and non-treated PLA muscles, and thus did not follow the changes in MHC isoforms. An increase in the mitochondrial CK isozyme activity (mi-CK) was shown in both non-treated and previously degenerated PLA muscles (123 and 117%, P< 0.01, respectively), without specific effect of regeneration. The ratio of mi-CK to CS activity, an estimate of the mitochondrial specific activity of mi-CK was significantly increased by training (P< 0.02) and decreased by regeneration (P< 0.05). Taken together, these data suggest that while training and regeneration have cumulative effects on the pattern of fast MHC expression, the training-induced changes in the energy metabolism shown in mature non-treated myofibres are similar to those observed in regenerated fibres.
- Published
- 2000
- Full Text
- View/download PDF
9. Immunosuppressive Treatment Affects Cardiac and Skeletal Muscle Mitochondria by the Toxic Effect of Vehicle
- Author
-
Sanchez, H., Bigard, X., Veksler, V., Mettauer, B., Lampert, E., Lonsdorfer, J., and Ventura-Clapier, R.
- Abstract
In order to examine whether immunosuppressive treatment could be responsible for the reduced exercise capacity of heart transplant recipients (HTR), we studied the effects of long-term immunosuppressive treatment with cyclosporin A (CsA) and its vehicle (2/3 cremophor and 1/3 alcohol diluted in olive oil) on in situmitochondrial respiration of different muscles. Rats were fed for 3 weeks with 10 or 25 mg/kg/day CsA in its vehicle (CsA10 and CsA25 groups), or vehicle or H2O. Oxygen consumption rate was measured in saponin skinned fibers without (V0) and with ADP until maximal respiration (Vmax) was reached and KMfor ADP as well as Vmaxwere calculated using non-linear fit of the Michaelis–Menten equation. In the cardiac muscle of the CsA25 group, V0and Vmaxwere decreased by immunosuppressive treatment respectively from 6.33±0.51 to 3.18±0.3μmol O2/min/g dw (P<0.001) and from 29.0±1.5 to 18.1±1.6μmol O2/min/g dw (P<0.001), an effect which could be entirely attributed to the vehicle itself, with no difference between CsA10 and CsA25. Regulation of cardiac mitochondrial respiration by ADP was altered by vehicle with the KMfor ADP decreasing from 371±37 to 180±21μm(P<0.001). A similar trend was observed in the diaphragm or soleus, although to a lesser extent. In contrast, V0and Vmaxdecreased in glycolytic gastrocnemius muscle respectively from 1.7±0.2 to 0.94±0.14 (P<0.01) and from 6.8±0.3 to 5.1±0.4μmol O2/min/g dw (P<0.001) in the CsA25 group, but the main effects could be attributed to CsA itself. It was concluded that immunosuppressive treatment induces a deleterious effect on cardiac and skeletal muscle oxidative capacities, mainly due to cremophor, the main component of vehicle.
- Published
- 2000
- Full Text
- View/download PDF
10. Cellular energetic metabolism: physiological and pathological aspects
- Author
-
Sztark, F., Payen, J. F., Piriou, V., Rigoulet, M., Ventura-Clapier, R., Mazat, J. P., Leverve, X., and Janvier, G.
- Published
- 1999
- Full Text
- View/download PDF
11. Muscle Unloading Induces Slow to Fast Transitions in Myofibrillar but not Mitochondrial Properties. Relevance to Skeletal Muscle Abnormalities in Heart Failure
- Author
-
Bigard, A.-X., Boehm, E., Veksler, V., Mateo, P., Anflous, K., and Ventura-Clapier, R.
- Abstract
Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessedin situin saponin skinned fibers (12.5±0.8 in C and 15.1±0.9μmol O2/min/g dw in HS soleus compared to 7.3±1.3μmol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Kmfor ADP of mitochondrial respiration, either in the absence (511±92 in C and 511±111μmin HS soleus compared to 9±4μMin control EDL) or presence of creatine (88±10 in C and 95±16μmin HS soleus compared to 32±9μMin control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.
- Published
- 1998
- Full Text
- View/download PDF
12. Muscle creatine kinase-deficient mice. II. Cardiac and skeletal muscles exhibit tissue-specific adaptation of the mitochondrial function.
- Author
-
Veksler, V I, Kuznetsov, A V, Anflous, K, Mateo, P, van Deursen, J, Wieringa, B, and Ventura-Clapier, R
- Abstract
Functional properties of in situ mitochondria and of mitochondrial creatine kinase were studied in saponin-skinned fibers taken from normal and M-creatine kinase-deficient mice. In control animals, apparent Km values of mitochondrial respiration for ADP in cardiac (ventricular) and slow-twitch (soleus) muscles (137 +/- 16 microM and 209 +/- 10 microM, respectively) were manyfold higher than that in fast-twitch (gastrocnemius) muscle (7.5 +/- 0.5 microM). Creatine substantially decreased the Km values only in cardiac and slow-twitch muscles (73 +/- 11 microM and 131 +/- 21 microM, respectively). As compared to control, in situ mitochondria in transgenic ventricular and slow-twitch muscles showed two times lower Km values for ADP, and the presence of creatine only slightly decreased the Km values. In mutant fast-twitch muscle, a decrease rather than increase in mitochondrial sensitivity to ADP occurred, but creatine still had no effect. Furthermore, in these muscles, relatively low oxidative capacity was considerably elevated. It is suggested that in the mutant mice, impairment of energy transport function in ventricular and slow-twitch muscles is compensated by a facilitation of adenine nucleotide transportation between mitochondria and cellular ATPases; in fast-twitch muscle, mainly energy buffering function is depressed, and that is overcome by an increase in energy-producing potential.
- Published
- 1995
13. Muscle creatine kinase-deficient mice. I. Alterations in myofibrillar function.
- Author
-
Ventura-Clapier, R, Kuznetsov, A V, d'Albis, A, van Deursen, J, Wieringa, B, and Veksler, V I
- Abstract
The regulation of contractile activity in mice bearing a null mutation of the M-isoform of creatine kinase gene, has been investigated in tissue extracts and Triton X-100-treated preparations of ventricular, soleus, and gastrocnemius muscles of control and transgenic mice. Skinned fiber experiments did not evidence any statistical difference in the maximal force or the calcium sensitivity of either muscle type. Rigor tension development at a low MgATP concentration was greatly influenced by phosphocreatine in control but not in transgenic mice as should be expected. In calcium-activated ventricular preparations, although the force developed by each cross-bridge was the same in control and transgenic animals, the rate constant of tension changes appeared to be markedly slowed in transgenic animals. As the ventricular isomyosin pattern was not altered, we suggested that, in transgenic animals, cross-bridge cycling was hindered by a local decrease in the MgATP to MgADP ratio, due to lack of a local MgATP regenerating system. Myokinase activity was not significantly changed while activities of pyruvate kinase or glyceraldehyde-3-phosphate dehydrogenase were found to be increased in transgenic animals. These results show that no fundamental remodelling occurs in myofibrils of transgenic animals but that important adaptations modify the bioenergetic pathways including glycolytic metabolism.
- Published
- 1995
14. Compartmentation of creatine kinase isoenzymes in myometrium of gravid guinea‐pig.
- Author
-
Clark, J F, Khuchua, Z, Kuznetsov, A, Saks, V A, and Ventura‐Clapier, R
- Abstract
1. This study was performed to investigate the possible presence and role of the creatine kinase (CK) system in the contraction and relaxation of skinned guinea‐pig uterus as well as the changes of the CK system during gestation. Experiments were performed on isolated longitudinal fibres of gravid and non‐gravid myometrium. 2. Total CK activity increased from 74 +/‐ 11 to 196 +/‐ 39 IU (g wet wt)‐1 during gestation. 3. The four isoenzymes of CK: muscle (MM), muscle‐brain (MB), brain (BB) and mitochondrial (mt‐CK) were found in myometrium. MM, MB and BB isoenzymes represented respectively 20.3 +/‐ 2.6, 10.3 +/‐ 4.4 and 72.7 +/‐ 2.2% of total activity. The distribution of isoenzymes did not significantly change with gestation, the contribution of mt‐CK increasing from trace to 5% of total activity. 4. BB‐CK was specifically bound to Triton X‐100‐skinned fibres with the non‐gravid uterus containing 6.7 +/‐ 1.9 IU (g wet wt)‐1 and the gravid uterus containing 44 +/‐ 13 IU (g wet wt)‐1. 5. Active tension of Triton X‐100‐treated fibres increased from 6.06 +/‐ 0.68 to 19.3 +/‐ 1.9 mM mm‐2 during gestation. 6. Submaximal tension (43.3 +/‐ 4.4% of maximal tension) can be developed in the absence of ATP and in the presence of 12 mM phosphocreatine (PCr) and 250 microM MgADP from endogenous CK in non‐gravid uterine fibres while the gravid uterus was able to generate 65.4 +/‐ 3.9% of maximal tension via the CK system. 7. The endogenous CK system was able to relax the skinned fibres from high‐tension rigor conditions by 47.3 +/‐ 4.2% of total relaxation in non‐gravid fibres and 60.6 +/‐ 3.2% of total relaxation in gravid fibres. 8. Non‐gravid and gravid uteri both contained mt‐CK of 17.5 +/‐ 8.4 and 140 +/‐ 22 micrograms (g wet wt)‐1 respectively as determined with antibodies against mt‐CK. 9. Oxygen consumption was studied in fibres where the plasmalemma was solubilized with 50 micrograms ml‐1 saponin. Maximal respiration was increased from 0.91 +/‐ 0.05 to 2.61 +/‐ 0.16 mumol oxygen min‐1 (g dry wt)‐1 in the gravid uterine fibres. However, creatine did not stimulate respiration in the uterine fibres treated with saponin. 10. It is concluded that the CK system undergoes qualitative as well as quantitative changes during gestation. BB‐CK is specifically localized in the myofilaments and mt‐CK is present in the uterine mitochondria.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1993
- Full Text
- View/download PDF
15. Dependence upon high-energy phosphates of the effects of inorganic phosphate on contractile properties in chemically skinned rat cardiac fibres
- Author
-
Mekhfi, H. and Ventura-Clapier, R.
- Abstract
The effects of inorganic phosphate (P
i ) on mechanical properties of Triton X100 treated ventricular fibres have been studied in different substrate conditions. In the presence of both MgATP and phosphacreatine, increasing concentrations of Pi progressively decreased maximal active force, up to 50–60% at 20 mM Pi . The reduction in stiffness was slightly less. These effects appeared nearly independent of the diameter of the preparations. 20 mM Pi decreased Ca sensitivity of the myofilaments and increased the Hill coefficient of the tension/pCa relationship; furthermore, the time constant of tension recovery was decreased from 12.9 to 8.9 ms suggesting that the cycling rate of cross-bridges was increased in the presence of Pi . When MgATP was regenerated by the myofilament bound creatine kinase in the presence of phosphocreatine, Pi was less efficient in decreasing the maximal tension and it weakened the relaxing effect of MgATP upon rigor tension. These effects are related to the inhibition of creatine kinase by Pi . The effects of Pi on maximal force and kinetics of contraction were antagonized by the effects of a decrease in phosphocreatine. The results are discussed in terms of the antagonistic role of Pi increase and phosphocreatine decrease upon contractile properties of myofilaments during hypoxia in heart muscle.- Published
- 1988
- Full Text
- View/download PDF
16. Reversible MM-creatine kinase binding to cardiac myofibrils
- Author
-
Ventura-Clapier, R., Saks, V. A., Vassort, G., Lauer, C., and Elizarova, G. V.
- Abstract
Skinned rat papillary muscles and purified preparations of rat cardiac myofibrils were used to study the nature of the interaction of creatine kinase with cardiac myofibrils. High activity of creatine kinase (2 IU/mg protein in fibers and 0.9 IU/mg in purified myofibrils) was due mostly to reversibly bound enzyme. This activity could be removed and rebound. The process of creatine kinase rebinding was characterized by apparent Km value of 0.14 mg/ml (approximately equal to 2 X 10(6) M). Rebinding of creatine kinase to cardiac myofibrils restored the phenomenon of functional compartmentation of adenine nucleotides in myofibrillar space and restored the ability of phosphocreatine to decrease the rigor tension in the presence of MgADP. The physiological experiments with quick length changes showed that rebinding of creatine kinase to skinned papillary muscle also restored Ca sensitivity, increased maximal tension development, decreased stiffness, and restored the tension recovery after quick length changes in muscle under condition of inhibition of endogenous creatine kinase by 1-fluoro-2,4-dinitrobenzene. It is concluded that creatine kinase reversibly bound to cardiac myofibrils is involved in the energy supply for cardiac contraction.
- Published
- 1987
- Full Text
- View/download PDF
17. Functional coupling of creatine kinases in muscles: Species and tissue specificity
- Author
-
Ventura-Clapier, R., Kuznetsov, A., Veksler, V., Boehm, E., and Anflous, K
- Abstract
Creatine kinase (CK) isoenzymes are present in all vertebrates. An important property of the creatine kinase system is that its total activity, its isoform distribution, and the concentration of guanidino substrates are highly variable among species and tissues. In the highly organized structure of adult muscles, it has been shown that specific CK isoenzymes are bound to intracellular compartments, and are functionally coupled to enzymes and transport systems involved in energy production and utilization. It is however, not established whether functional coupling and intracellular compartmentation are present in all vertebrates. Furthermore, these characteristics seem to be different among different muscle types within a given species. This study will review some of these aspects. It has been observed that: (1) In heart ventricle, CK compartmentation and coupling characterize adult mammalian cells. It is almost absent in frogs, and is weakly present in birds. (2) Efficient coupling of MM-CK to myosin ATPase is seen in adult mammalian striated muscles but not in frog and bird heart where B-CK is expressed instead of M-CK. Thus, the functional efficacy of bound MM-CK to regulate adenine nucleotide turnover within the myofibrillar compartment seems to be specific for muscles expressing M-CK as an integral part of the sarcomere. (3) Mi-CK expression and/or functional coupling are highly tissue and species specific; moreover, they are subject to short term and long term adaptations, and are present late in development. The mitochondrial form of CK (mi-CK) can function in two modes depending on the tissue: (i) in an ≪ADP regeneration mode≫ and (ii) in an ≪ADP amplification mode≫. The mode of action of mi-CK seems to be related to its precise localization within the mitochondrial intermembrane space, whereas its amount might control the quantitative aspects of the coupling. Mi-CK is highly plastic, making it a strong candidate for fine regulation of excitation-contraction coupling in muscles and for energy transfer in cells with large and fluctuating energy demands in general. (4) Although CK isoforms show a binding specificity, the presence of a given isoform within a tissue or a species only, does not predict its functional role. For example, M-CK is expressed before it is functionally compartmentalized within myofibrils during development. Similarly, the presence of ubiquitous or sarcomeric mi-CK isoforms, is not an index of functional coupling of mi-CK to oxidative phosphorylation. (5) Amongst species or muscles, it appears that a large buffering action of the CK system is associated with rapid contraction and high glycolytic activity. On the other hand, an oxidative metabolism is associated with isoform diversity, increased compartmentation, a subsequent low buffering action and efficient phosphotransfer between mitochondria and energy utilization sites. It can be concluded that, in addition to a high variation of total activity and isoform expression, the role of the CK system also critically depends on its intracellular organization and interaction with energy producing and utilizing pathways. This compartmentation will determine the high cellular efficiency and fine specialization of highly organized and differentiated muscle cells.
- Published
- 1998
- Full Text
- View/download PDF
18. On the regulation of cellular energetics in health and disease
- Author
-
Saks, V. A., Tiivel, T., Kay, L., Novel-Chaté, V, Daneshrad, Z., Rossi, A., Fontaine, E., Keriel, C., Leverve, X., Ventura-Clapier, R., Anflous, K., Samuel, J. -L., and Rappaport, L.
- Abstract
Very recent experimental data, obtained by using the permeabilized cell technique or tissue homogenates for investigation of the mechanisms of regulation of respiration in the cells in vivo, are shortly summarized. In these studies, surprisingly high values of apparent Km for ADP, exceeding that for isolated mitochondria in vitro by more than order of magnitude, were recorded for heart, slow twitch skeletal muscle, hepatocytes, brain tissue homogenates but not for fast twitch skeletal muscle. Mitochondrial swelling in the hypo-osmotic medium resulted in the sharp decrease of the value of Km for ADP in correlation with the degree of rupture of mitochondrial outer membrane, as determined by the cytochrome c test. Very similar effect was observed when trypsin was used for treatment of skinned fibers, permeabilized cells or homogenates. It is concluded that, in many but not all types of cells, the permeability of the mitochondrial outer membrane for ADP is controlled by some cytoplasmic protein factor(s). Since colchicine and taxol were not found to change high values of the apparent Km for ADP, the participation of microtubular system seems to be excluded in this kind of control of respiration but studies of the roles of other cytoskeletal structures seem to be of high interest.
- Published
- 1996
- Full Text
- View/download PDF
19. Role of creatine kinase in force development in chemically skinned rat cardiac muscle.
- Author
-
Ventura-Clapier, R, Mekhfi, H, and Vassort, G
- Abstract
The influence of phosphocreatine in the presence or absence of MgATP and MgADP was studied in Triton X-100-treated thin papillary muscles and ventricular strips of the rat heart. The pCa/tension relationships, the pMgATP/tension relationships, and the tension responses to quick length changes were analyzed. The results show three major consequences of the reduction of the phosphocreatine concentration in the presence of millimolar concentrations of the MgATP. (a) The resting tension and the maximal Ca2+-activated tension were increased, and the pCa/tension relationship was shifted toward higher pCa values and its steepness was decreased; these effects were enhanced by the inclusion of MgADP. (b) The time constant of tension recoveries after quick stretches applied during maximal activation was increased, while the extent of these recoveries was decreased. (c) The study of pMgATP/tension relationships in low Ca concentrations showed that the decrease in phosphocreatine induced a shift toward higher MgATP values with no changes in maximal rigor tension or the slope coefficient; these effects were increased by the increase in MgADP and were independent of the preparation diameter. Thus, modifications of the apparent Ca sensitivity and resting and maximal tension when phosphocreatine is decreased seem to be due to an increasing participation of rigor-like or slowly cycling cross-bridges spending more time in the attached state. These results suggest that endogenous creatine kinase is able to ensure maximal efficiency of myosin ATPase by producing a local high MgATP/MgADP ratio.
- Published
- 1987
- Full Text
- View/download PDF
20. Nitric oxide inhibits cardiac energy production via inhibition of mitochondrial creatine kinase
- Author
-
Kaasik, A., Minajeva, A., Sousa, E. De, Ventura-Clapier, R., and Veksler, V.
- Published
- 1999
- Full Text
- View/download PDF
21. Etude des mecanismes de la dysfunction myocardique au cours du choc endotoxinique
- Author
-
Tavernier, B, Lenoble, C, Mebazaa, A, Veksler, V, Payen, D, and Ventura-Clapier, R
- Published
- 1997
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.