β2-Agonist administration increases sarcoplasmic reticulum Ca2+-ATPase activity in aged rat skeletal muscle

2005 ◽  
Vol 288 (3) ◽  
pp. E526-E533 ◽  
Author(s):  
Jonathan D. Schertzer ◽  
David R. Plant ◽  
James G. Ryall ◽  
Felice Beitzel ◽  
Nicole Stupka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Time Course ◽  
Fiber Type ◽  
Critical Role ◽  
Maximal Activity ◽  
Contractile Properties ◽  
Kinetic Properties ◽  
Protein Levels ◽  
Age Related

Aging is associated with a slowing of skeletal muscle contractile properties, including a decreased rate of relaxation. In rats, the age-related decrease in the maximal rate of relaxation is reversed after 4-wk administration with the β2-adrenoceptor agonist (β2-agonist) fenoterol. Given the critical role of the sarcoplasmic reticulum (SR) in regulating intracellular Ca2+ transients and ultimately the time course of muscle contraction and relaxation, we tested the hypothesis that the mechanisms of action of fenoterol are mediated by alterations in SR proteins. Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) kinetic properties were assessed in muscle homogenates and enriched SR membranes isolated from the red (RG) and white (WG) portions of the gastrocnemius muscle in adult (16 mo) and aged (28 mo) F344 rats that had been administered fenoterol for 4 wk (1.4 mg/kg/day ip, in saline) or vehicle only. Aging was associated with a 29% decrease in the maximal activity ( Vmax) of SERCA in the RG but not in the WG muscles. Fenoterol treatment increased the Vmax of SERCA and SERCA1 protein levels in RG and WG. In the RG, fenoterol administration reversed an age-related selective nitration of the SERCA2a isoform. Our findings demonstrate that the mechanisms underlying age-related changes in contractile properties are fiber type dependent, whereas the effects of fenoterol administration are independent of age and fiber type.

scholarly journals Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo

2017 ◽  
Vol 114 (45) ◽  
pp. E9559-E9568 ◽  
Author(s):  
Qing He ◽  
Richard Bouley ◽  
Zun Liu ◽  
Marc N. Wein ◽  
Yan Zhu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
G Protein ◽  
Critical Role ◽  
Hek293 Cells ◽  
Activity Levels ◽  
Α Subunit ◽  
Proteomic Screen ◽  
Protein Levels ◽  
G Protein Α Subunit

Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS, XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it. Similarly, primary cardiomyocytes derived from XLαs knockout (XLKO) pups showed enhanced transferrin internalization. Early postnatal XLKO mice showed a significantly higher degree of cardiac iron uptake than wild-type littermates following iron dextran injection. In XLKO neonates, iron and ferritin levels were elevated in heart and skeletal muscle, where XLαs is normally expressed abundantly. XLKO heart and skeletal muscle, as well as XLKO Ocy454 cells, showed elevated SNX9 protein levels, and siRNA-mediated knockdown of SNX9 in XLKO Ocy454 cells prevented enhanced transferrin internalization. In transfected cells, XLαs also inhibited internalization of the parathyroid hormone and type 2 vasopressin receptors. Internalization of transferrin and these G protein-coupled receptors was also inhibited in cells expressing an XLαs mutant missing the Gα portion, but not Gsα or an N-terminally truncated XLαs mutant unable to interact with SNX9 or dynamin. Thus, XLαs restricts clathrin-mediated endocytosis and plays a critical role in iron/transferrin uptake in vivo.

No limiting role for glycogenin in determining maximal attainable glycogen levels in rat skeletal muscle

2000 ◽  
Vol 278 (3) ◽  
pp. E398-E404 ◽  
Author(s):  
Bo Falck Hansen ◽  
Wim Derave ◽  
Pia Jensen ◽  
Erik A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Level ◽  
Fiber Type ◽  
Rat Skeletal Muscle ◽  
Protein Core ◽  
Protein Levels ◽  
Very High ◽  
White Gastrocnemius

We examined whether the protein level and/or activity of glycogenin, the protein core upon which glycogen is synthesized, is limiting for maximal attainable glycogen levels in rat skeletal muscle. Glycogenin activity was 27.5 ± 1.4, 34.7 ± 1.7, and 39.7 ± 1.3 mU/mg protein in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. A similar fiber type dependency of glycogenin protein levels was seen. Neither glycogenin protein level nor the activity of glycogenin correlated with previously determined maximal attainable glycogen levels, which were 69.3 ± 5.8, 137.4 ± 10.1, and 80.0 ± 5.4 μmol/g wet wt in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. In additional experiments, rats were exercise trained by swimming, which resulted in a significant increase in the maximal attainable glycogen levels in soleus muscles (∼25%). This increase in maximal glycogen levels was not accompanied by an increase in glycogenin protein level or activity. Furthermore, even in the presence of very high glycogen levels (∼170 μmol/g wet wt), ∼30% of the total glycogen pool continued to be present as unsaturated glycogen molecules (proglycogen). Therefore, it is concluded that glycogenin plays no limiting role for maximal attainable glycogen levels in rat skeletal muscle.

scholarly journals Aging and muscle fiber type alter K+ channel contributions to the myogenic response in skeletal muscle arterioles

2009 ◽  
Vol 107 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Lori S. Kang ◽  
SeJeong Kim ◽  
James M. Dominguez ◽  
Amy L. Sindler ◽  
Gregory M. Dick ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Negative Feedback ◽  
Vascular Tone ◽  
Fiber Type ◽  
Myogenic Tone ◽  
Myogenic Response ◽  
Fiber Types ◽  
Age Related ◽  
Myogenic Regulation ◽  
Regulation Of Vascular Tone

Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent evidence indicates that both large-conductance Ca2+-activated (BKCa) and voltage-dependent (KV) K+ channels mediate negative feedback control of the myogenic response. Thus we tested the hypothesis that aging increases the contributions of KV and BKCa channels to myogenic regulation of vascular tone. Because myogenic responsiveness differs between oxidative and glycolytic muscles, we predicted that KV and BKCa channel contributions to myogenic responsiveness vary with fiber type. Myogenic responses of first-order arterioles from the gastrocnemius and soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors of KV and BKCa, respectively. 4-Aminopyridine enhanced myogenic tone with aging and normalized age-related differences in both muscle types. By contrast, iberiotoxin eliminated age-related differences in soleus arterioles and had no effect in gastrocnemius vessels. KV1.5 is an integral component of KV channels in vascular smooth muscle; therefore, we determined the relative protein expression of KV1.5, as well as BKCa, in soleus and gastrocnemius arterioles. Immunoblot analysis revealed no differences in KV1.5 protein with aging or between variant fiber types, whereas BKCa protein levels declined with age in arterioles from both muscle groups. Collectively, these results suggest that the contribution of BKCa to myogenic regulation of vascular tone changes with age in soleus muscle arterioles, whereas increased KV channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.

scholarly journals Adaptations in human muscle sarcoplasmic reticulum to prolonged submaximal training

2003 ◽  
Vol 94 (5) ◽  
pp. 2034-2042 ◽  
Author(s):  
H. J. Green ◽  
C. S. Ballantyne ◽  
J. D. MacDougall ◽  
M. A. Tarnopolsky ◽  
J. D. Schertzer
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Vastus Lateralis ◽  
Training Session ◽  
Maximal Activity ◽  
Hill Coefficient ◽  
Protein Levels ◽  
Plasmic Reticulum ◽  
Cycle Training ◽  
The Hill

In this study, we employed single-leg submaximal cycle training, conducted over a 10-wk period, to investigate adaptations in sarcoplasmic reticulum (SR) Ca2+-regulatory proteins and processes of the vastus lateralis. During the final weeks, the untrained volunteers (age 21.4 ± 0.3 yr; means ± SE, n = 10) were exercising 5 times/wk and for 60 min/session. Analyses were performed on tissue extracted by needle biopsy ∼4 days after the last training session. Compared with the control leg, the trained leg displayed a 19% reduction ( P < 0.05) in homogenate maximal Ca2+-ATPase activity (192 ± 11 vs. 156 ± 18 μmol · g protein−1 · min−1), a 4.3% increase ( P < 0.05) in pCa50, defined as the Ca2+ concentration at half-maximal activity (6.01 ± 0.05 vs. 6.26 ± 0.07), and no change in the Hill coefficient (1.75 ± 0.15 vs. 1.76 ± 0.21). Western blot analysis using monoclonal antibodies (7E6 and A52) revealed a 13% lower ( P < 0.05) sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 in trained vs. control in the absence of differences in SERCA2a. Training also resulted in an 18% lower ( P < 0.05) SR Ca2+ uptake and a 26% lower ( P < 0.05) Ca2+ release. It is concluded that a downregulation in SR Ca2+ cycling in vastus lateralis occurs with aerobic-based training, which at least in the case of Ca2+ uptake can be explained by reduction in Ca2+-ATPase activity and SERCA1 protein levels.

Parvalbumin relaxes frog skeletal muscle when sarcoplasmic reticulum Ca(2+)-ATPase is inhibited

1996 ◽  
Vol 270 (2) ◽  
pp. C411-C417 ◽  
Author(s):  
Y. Jiang ◽  
J. D. Johnson ◽  
J. A. Rall
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Relaxation Rate ◽  
Time Course ◽  
Muscle Fibers ◽  
Peak Force ◽  
Half Time ◽  
Frog Skeletal Muscle ◽  
Twitch Force ◽  
Total Failure

Inhibition of sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) in frog skeletal muscle fibers at 10 degrees C prolonged the half time of the fall of the Ca2+ transient by 62% and twitch force by 100% and increased peak force by 120% without increasing the amplitude of the Ca2+ signal. In the presence of TBQ the rate of relaxation and the rate of fall of Ca2+ became progressively slower in a series of twitches until relaxation failed. Relaxation rate decreased with a time course (approximately 2 s-1) similar to the Mg2+ off rate from purified parvalbumin (PA; 3.6 s-1). TBQ slowed the rate of fall of Ca2+ (5-fold) and force (8-fold) in a 0.3-s tetanus so that the rate of fall of Ca2+ (approximately 2.5 s-1) was similar to the Mg2+ off rate from PA. TBQ caused a near total failure of both Ca2+ sequestration and relaxation in a 1.1-s tetanus, during which PA would be saturated with Ca2+ and could not contribute to relaxation. Thus, when the SR Ca(2+)-ATPase is inhibited, Mg(2+)-PA can sequester Ca2+ and produce relaxation at a rate that is defined by the Mg2+ off rate from PA.

Age-related chemical modification of the skeletal muscle sarcoplasmic reticulum Ca-ATPase of the rat

1999 ◽  
Vol 107 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Christian Schöneich ◽  
Rosa I. Viner ◽  
Deborah A. Ferrington ◽  
Diana J. Bigelow
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Chemical Modification ◽  
Age Related

scholarly journals Intrinsic aerobic capacity correlates with greater inherent mitochondrial oxidative and H2O2 emission capacities without major shifts in myosin heavy chain isoform

2012 ◽  
Vol 113 (10) ◽  
pp. 1624-1634 ◽  
Author(s):  
Erin L. Seifert ◽  
Mark Bastianelli ◽  
Céline Aguer ◽  
Cynthia Moffat ◽  
Carmen Estey ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Environmental Changes ◽  
Disease Risk ◽  
Fiber Type ◽  
High Capacity ◽  
Oxidative Modification ◽  
Treadmill Running ◽  
Myosin Heavy Chain Isoform ◽  
Protein Levels ◽  
And Performance

Exercise capacity and performance strongly associate with metabolic and biophysical characteristics of skeletal muscle, factors that also relate to overall disease risk. Despite its importance, the exact mechanistic features that connect aerobic metabolism with health status are unknown. To explore this, we applied artificial selection of rats for intrinsic (i.e., untrained) aerobic treadmill running to generate strains of low- and high-capacity runners (LCR and HCR, respectively), subsequently shown to diverge for disease risk. Concurrent breeding of LCR and HCR per generation allows the lines to serve as reciprocal controls for unknown environmental changes. Here we provide the first direct evidence in mitochondria isolated from skeletal muscle that intrinsic mitochondrial capacity is higher in HCR rats. Maximal phosphorylating respiration was ∼40% greater in HCR mitochondria, independent of substrate and without altered proton leak or major changes in protein levels or muscle fiber type, consistent with altered control of phosphorylating respiration. Unexpectedly, H2O2 emission was ∼20% higher in HCR mitochondria, due to greater reduction of more harmful reactive oxygen species to H2O2; indeed, oxidative modification of mitochondrial proteins was lower. When the higher mitochondrial yield was considered, phosphorylating respiration and H2O2 emission were 70–80% greater in HCR muscle. Greater capacity of HCR muscle for work and H2O2 signaling may result in enhanced and more immediate cellular repair, possibly explaining lowered disease risks.

Ischemia-induced alterations in sarcoplasmic reticulum Ca(2+)-ATPase activity in rat soleus and EDL muscles

1996 ◽  
Vol 271 (6) ◽  
pp. C1942-C1948 ◽  
Author(s):  
H. J. Green ◽  
N. H. McKee ◽  
A. J. Carvalho ◽  
J. C. Dossett-Mercer
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Time Course ◽  
Extensor Digitorum Longus ◽  
Fiber Type ◽  
Time Dependent ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Edl Muscle ◽  
Muscle Fiber Type Composition

To investigate the time-dependent effects of ischemia, as modified by muscle fiber type composition, on sarcoplasmic reticulum (SR) function, Ca(2+)-ATPase activity (total minus basal) was measured in homogenates prepared from samples obtained from rat soleus and extensor digitorum longus (EDL) muscle of ischemic and contralateral controls. Ischemia was induced by occlusion of blood flow to one hindlimb for periods of 1, 2, and 3 h (n = 10 per group). In EDL, maximal Ca(2+)-ATPase activity (expressed in mumol.g wet wt-1.min-1) was higher (P < 0.05) in ischemic than in control at 1 h (80 +/- 10 vs. 56.5 +/- 5.3) and increased progressively with ischemia at both 2 h (88 +/- 4.6 vs. 53.1 +/- 2.8) and 3 h (116 +/- 3.8 vs. 67.8 +/- 3.2). In contrast, in soleus, increases (P < 0.05) in Ca(2+)-ATPase activity with ischemia were observed at 2 h (19.2 +/- 0.86 vs. 14.0 +/- 0.56) and 3 h (19.9 +/- 1.4 vs. 12.4 +/- 0.62) but not at 1 h (10.7 +/- 1.5 vs. 10.0 +/- 0.83). In both EDL and soleus, basal Mg(2+)-ATPase was unchanged with ischemia. On the basis of these findings, it can be concluded that ischemia results in an increase in the maximal SR Ca(2+)-ATPase activity but that the time course of the change is dependent on the fiber type composition of the muscle.

Effects of aging on sarcoplasmic reticulum function and contraction duration in skeletal muscles of the rat

1996 ◽  
Vol 271 (4) ◽  
pp. C1032-C1040 ◽  
Author(s):  
N. Narayanan ◽  
D. L. Jones ◽  
A. Xu ◽  
J. C. Yu
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Soleus Muscle ◽  
Pump Function ◽  
Related Difference ◽  
Contraction Duration ◽  
Age Related ◽  
Isometric Twitch ◽  
Effects Of Aging ◽  
The Impact

The impact of aging on the Ca2+ pump function of skeletal muscle sarcoplasmic reticulum (SR) was investigated using SR-enriched membrane vesicles isolated from the slow-twitch soleus muscle (SM) and the relatively fast-twitch gastrocnemius muscle (GM) isolated from adult (6-8 mo old) and aged (26-28 mo old) Fischer 344 rats. In addition, isometric twitch characteristics of SM and GM were determined in situ in adult and aged rats under anesthesia. The rates of ATP-supported Ca2+ uptake by SM SR was markedly lower ( approximately 50%) in the aged compared with adult at varying Ca2+ (0.11-8.24 microM) concentrations. Kinetic analysis of the data revealed age-associated decrease in maximum activity reached (Vmax) and increase in the concentration of Ca2+ giving half of Vmax. In contrast, no significant age-related difference was observed in ATP-supported Ca2+ uptake activity of GM SR. The Ca(2+)-stimulated adenosinetriphosphatase (ATPase) activities and the amount of Ca(2+)-ATPase protein did not vary significantly with aging in SM or GM SR. Also, no significant age-related difference was observed in the content of the ryanodine receptor (Ca(2+)-release channel) or the Ca2+ binding protein, calsequestrin in SM and GM SR. In isometrically contracting SM, the time to peak force, half-relaxation time, and contraction duration were significantly prolonged in the aged compared with adult, whereas there was no age-related difference in maximum developed force. None of these isometric twitch parameters differed significantly with age in the GM. These results demonstrate that the effects of aging on skeletal muscle contractile properties and SR function are muscle specific. Furthermore, the data strongly suggest that impairment in SR Ca2+ pump function, apparently due to uncoupling of ATP hydrolysis from Ca2+ transport, contributes to the age-associated slowing of relaxation in the soleus muscle.

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