Contractile and metabolic effects of increased creatine kinase activity in mouse skeletal muscle

1996 ◽  
Vol 270 (4) ◽  
pp. C1236-C1245 ◽  
Author(s):  
B. B. Roman ◽  
J. M. Foley ◽  
R. A. Meyer ◽  
A. P. Koretsky
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Kinase Activity ◽  
Contractile Function ◽  
Contractile Activity ◽  
High Energy ◽  
Metabolic Effects ◽  
High Energy Phosphates ◽  
Lactate Dehydrogenase Activity ◽  
B Subunit

The effects of increased expression of creatine kinase (CK) in skeletal muscle were studied in control and transgenic animals homozygous for expression of the B subunit of CK. CK activity was 47% higher in transgenic gastrocnemius muscle. The CK activity was distributed as follows: 45 +/- 1% MM dinner, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. No significant differences in metabolic or contractile proteins were detected except for a 22% decrease in lactate dehydrogenase activity and a 9% decrease in adenylate kinase activity. The only significant effect in contractile activity was that the rise time of a 5-s isometric contraction was 28% faster in the transgenic muscle. 31P nuclear magnetic resonance (NMR) spectra were obtained from control and transgenic muscles during mechanical activation, and there were no NMR measurable differences detected. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effects on skeletal muscle metabolism or contractile function. Therefore, control muscle has sufficient CK activity to keep up with changes in cellular high-energy phosphates except during the early phase of intense contractile activity.

Cardiac force and high-energy phosphates under metabolic inhibition in four ectothermic vertebrates

1996 ◽  
Vol 271 (4) ◽  
pp. R946-R954 ◽  
Author(s):  
T. Hartmund ◽  
H. Gesser
Keyword(s):  
Creatine Kinase ◽  
Atpase Activity ◽  
Kinase Activity ◽  
Energy State ◽  
High Energy ◽  
Creatine Kinase Activity ◽  
The Other ◽  
Freshwater Turtle ◽  
High Energy Phosphates ◽  
Isometric Twitch

Isometric twitch tension of ventricular preparations stimulated at 0.2 Hz fell over 30 min of anoxia by a fraction decreasing in the order rainbow trout, cod, eel, and freshwater turtle. Drops in the estimated cytoplasmic energy state were related to larger tension losses for trout than for the other species, possibly due to larger changes in free phosphate. Anoxic energy degradation was slower for turtle than for the other species. Anoxia combined with glycolytic inhibition (1 mmol/l iodoacetate) enhanced the decrease in twitch tension for a drop in energy state and enlarged the increase in ADP/ATP relative to that in creatine/phosphocreatine to an extent inversely related to the creatine kinase activity. Furthermore, it increased resting tension to an extent possibly related to myosin-adenosinetriphosphatase (ATPase) activity and lowered the content of phosphorylated adenylates in trout and turtle myocardium. The results indicate that species differences in performance of the metabolically challenged myocardium depend on energy-degrading processes, e.g., myosin-ATPase activity, phosphate release, creatine kinase activity, and efflux/degradation of ADP and AMP, and that glycolysis offers protection due to its cytoplasmic localization.

Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin

2011 ◽  
Vol 436 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Zhe Chen ◽  
Tong-Jin Zhao ◽  
Jie Li ◽  
Yan-Song Gao ◽  
Fan-Guo Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Contraction ◽  
Binding Protein ◽  
High Energy ◽  
Functional Coupling ◽  
Muscle Type ◽  
Myosin Binding Protein ◽  
Slow Skeletal Muscle ◽  
Myosin Binding

Muscle contraction requires high energy fluxes, which are supplied by MM-CK (muscle-type creatine kinase) which couples to the myofibril. However, little is known about the detailed molecular mechanisms of how MM-CK participates in and is regulated during muscle contraction. In the present study, MM-CK is found to physically interact with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). The interaction between MyBPC1 and MM-CK depended on the creatine concentration in a dose-dependent manner, but not on ATP, ADP or phosphocreatine. The MyBPC1–CK interaction favoured acidic conditions, and the two molecules dissociated at above pH 7.5. Domain-mapping experiments indicated that MM-CK binds to the C-terminal domains of MyBPC1, which is also the binding site of myosin. The functional coupling of myosin, MyBPC1 and MM-CK is further corroborated using an ATPase activity assay in which ATP expenditure accelerates upon the association of the three proteins, and the apparent Km value of myosin is therefore reduced. The results of the present study suggest that MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (MM-CK) for efficient energy metabolism and homoeostasis.

Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading

1994 ◽  
Vol 266 (5) ◽  
pp. C1257-C1262 ◽  
Author(s):  
Y. Ohira ◽  
K. Saito ◽  
T. Wakatsuki ◽  
W. Yasui ◽  
T. Suetsugu ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Creatine Supplementation ◽  
High Energy ◽  
Hindlimb Suspension ◽  
Phosphorus Compounds ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Gravitational Unloading ◽  
Beta Adrenoceptor ◽  
Muscle Contractile

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

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)

Influence of intracellular acidosis on contractile function in the working rat heart

1987 ◽  
Vol 253 (6) ◽  
pp. H1499-H1505 ◽  
Author(s):  
F. M. Jeffrey ◽  
C. R. Malloy ◽  
G. K. Radda
Keyword(s):  
Stroke Volume ◽  
Intracellular Ph ◽  
Rat Heart ◽  
Contractile Function ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
Tension Development ◽  
O2 Delivery

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O2 delivery. Intracellular pH and high-energy phosphates were monitored by 31P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH4Cl (extracellular pH, 7.4). The subsequent washout of NH3 from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O2 consumption (rate-pressure product) and O2 delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca2+] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH2O) but were most prominent at the lowest external [Ca2+] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

Carbofuran-induced alterations (in vivo) in high-energy phosphates, creatine kinase (CK) and CK isoenzymes

1991 ◽  
Vol 65 (4) ◽  
pp. 304-310 ◽  
Author(s):  
Ramesh C. Gupta ◽  
John T. Goad ◽  
Wade L. Kadel
Keyword(s):  
Creatine Kinase ◽  
High Energy ◽  
High Energy Phosphates

scholarly journals Niacin protects the isolated heart from ischemia-reperfusion injury

2000 ◽  
Vol 279 (2) ◽  
pp. H764-H771 ◽  
Author(s):  
Nathan A. Trueblood ◽  
Ravichandran Ramasamy ◽  
Li Feng Wang ◽  
Saul Schaefer
Keyword(s):  
Creatine Kinase ◽  
Redox Regulation ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
High Energy ◽  
Low Flow ◽  
High Energy Phosphates ◽  
Zero Flow ◽  
Pyruvate Ratio

Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD+ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD+, would lower the NADH/NAD+ratio, increase glycolysis, and limit ischemic injury and 2) these cardioprotective benefits of niacin would be limited in conditions that block lactate removal. Isolated rat hearts were perfused without (Ctl) or with 1 μM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine the effects of limiting lactate efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero-flow ischemia and 2) the Nia group treated with the lactate-H+cotransport inhibitor α-cyano-4-hydroxycinnamate under LF conditions. Measured variables included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD+), lactate efflux rate, and creatine kinase release. The lactate-to-pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline and ischemic conditions ( P < 0.001 and P< 0.01, respectively), with concurrent lower creatine kinase release than Ctl hearts ( P < 0.05). Nia-LF hearts had significantly greater lactate release during ischemia ( P < 0.05 vs. Ctl hearts) as well as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with α-cyano-4-hydroxycinnamate and blocking lactate washout with zero flow negated some of the beneficial effects of niacin. During LF, niacin lowered the cytosolic redox state and increased lactate efflux, consistent with redox regulation of glycolysis. Niacin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeutic agent in patients with ischemic heart disease.

Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm

2005 ◽  
Vol 98 (5) ◽  
pp. 1753-1760 ◽  
Author(s):  
V. P. Wright ◽  
P. F. Klawitter ◽  
D. F. Iscru ◽  
A. J. Merola ◽  
T. L. Clanton
Keyword(s):  
Contractile Function ◽  
Force Production ◽  
Creatine Phosphate ◽  
High Energy ◽  
Diaphragm Muscle ◽  
Severe Hypoxia ◽  
High Energy Phosphates ◽  
Rat Diaphragm ◽  
Tetanic Force ◽  
Hypoxia Exposure

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of Pi. Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 μM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca2+ concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to ∼10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.

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