Dexamethasone up-regulates skeletal muscle maximal Na+,K+pump activity by muscle group specific mechanisms in humans

Sequential ischemia/reperfusion in a paired canine gracilis muscle model resulted in significant muscle salvage. In this model, one randomly chosen gracilis muscle was subjected to 5 h of ischemia followed by 48 h of in vivo reperfusion. The contralateral (second) muscle was then made ischemic and reperfused using the same protocol. Muscle necrosis was determined at the end of 48 h of reperfusion. A mean 60% reduction in muscle necrosis was observed in the second group of muscles. Analysis of tissue adenine nucleotides indicated that significant sparing of ATP utilization occurred in the second muscle group during ischemia. Preliminary analysis of tissue heat shock proteins (HSP) showed that the second group of muscles had a different pattern of HSP expression before the onset of ischemia. The results suggest that reduced ATP utilization and altered HSP expression in the second muscle play a role in the tissue salvage observed in this sequential muscle ischemia model.

Download Full-text

Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00361.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. C1438-C1444 ◽

Cited By ~ 16

Author(s):

Martin Broch-Lips ◽

Thomas Holm Pedersen ◽

Ole Bækgaard Nielsen

Keyword(s):

Skeletal Muscle ◽

Purinergic Receptor ◽

Purinergic Signaling ◽

Receptor Activation ◽

Control Force ◽

Fourfold Increase ◽

Pump Activity ◽

Force Recovery ◽

And Function ◽

Muscle Excitability

Activity-induced elevation of extracellular purines and pyrimidines has been associated with autocrine and paracrine signaling in many tissues. Here we investigate the effect of purinergic signaling for the excitability and contractility of depolarized skeletal muscle. Muscle excitability was experimentally depressed by elevating the extracellular K+ from 4 to 10 mM, which reduced the tetanic force to 24 ± 2% of the force at 4 mM K+. Upon addition of 1 mM ATP, however, the force recovered to 65 ± 8% of the control force ( P < 0.001, n = 5). A similar recovery was seen with ADP, but not with UTP or adenosine. The ATP-induced force recovery could be inhibited by P2Y1 receptor antagonists (3 μM SCH-202676 or 1 μM MRS-2500). A fourfold increase in M-wave area demonstrated that the ATP-induced force recovery was associated with restoration of muscle excitability ( P < 0.05, n = 4). Experiments using 86Rb+ as a tracer for K+ showed that ATP also induced a twofold increase in the activity of muscle Na+-K+ pumps. The force recovery and the stimulation of the Na+-K+ pump activity by ATP were inhibited by 50 μM of the phospholipase C inhibitor U-73122. It is concluded that purinergic signaling can increase the Na+-K+ pump activity and improve force and excitability of depolarized skeletal muscles. This novel purinergic regulation may be important for the maintenance of muscle excitability during intense exercise, where the extracellular K+ can increase substantially.

Download Full-text

Conserved and muscle-group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype

Physiological Genomics ◽

10.1152/physiolgenomics.00222.2003 ◽

2004 ◽

Vol 18 (2) ◽

pp. 184-195 ◽

Cited By ~ 22

Author(s):

Georgiana Cheng ◽

Anita P. Merriam ◽

Bendi Gong ◽

Patrick Leahy ◽

Sangeeta Khanna ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

System Development ◽

Expression Patterns ◽

Neuromuscular Diseases ◽

Local Environment ◽

Oculomotor System ◽

Muscle Group ◽

Specific Gene ◽

Extrinsic Factors

Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of the developmental regulation of the skeletal muscle phenotypic range. Here, we used morphological and DNA microarray analyses to generate a comprehensive temporal profile for rat EOM development. Based upon coordinate regulation of morphologic/gene expression traits with key events in visual, vestibular, and oculomotor system development, we propose a model that the EOM phenotype is a consequence of extrinsic factors that are unique to its local environment and sensory-motor control system, acting upon a novel myoblast lineage. We identified a broad spectrum of differences between the postnatal transcriptional patterns of EOM and limb muscle allotypes, including numerous transcripts not traditionally associated with muscle fiber/group differences. Several transcription factors were differentially regulated and may be responsible for signaling muscle allotype specificity. Significant differences in cellular energetic mechanisms defined the EOM and limb allotypes. The allotypes were divergent in many other functional transcript classes that remain to be further explored. Taken together, we suggest that the EOM allotype is the consequence of tissue-specific mechanisms that direct expression of a limited number of EOM-specific transcripts and broader, incremental differences in transcripts that are conserved by the two allotypes. This represents an important first step in dissecting allotype-specific regulatory mechanisms that may, in turn, explain differential muscle group sensitivity to a variety of metabolic and neuromuscular diseases.

Download Full-text

IN VITRO SKELETAL MUSCLE HYPERTROPHY AND Na PUMP ACTIVITY

Plasticity of Muscle ◽

10.1515/9783110837483-038 ◽

1980 ◽

pp. 493-506 ◽

Cited By ~ 5

Keyword(s):

Skeletal Muscle ◽

Muscle Hypertrophy ◽

Na Pump ◽

Skeletal Muscle Hypertrophy ◽

Pump Activity

Download Full-text

Molecular activity of sodium pumps in endotherms and ectotherms

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.5.r1287 ◽

1996 ◽

Vol 271 (5) ◽

pp. R1287-R1294 ◽

Cited By ~ 10

Author(s):

P. L. Else ◽

D. J. Windmill ◽

V. Markus

Keyword(s):

Skeletal Muscle ◽

Enzymatic Activity ◽

Direct Measurement ◽

Sodium Pump ◽

Turnover Rates ◽

Ouabain Binding ◽

General Increase ◽

Sodium Pumps ◽

Invertebrate Species ◽

Pump Activity

Previous research has shown ectotherms to have markedly lower sodium pump metabolism than endotherms. Direct measurement of enzymatic activity of the sodium pump (Na(+)-K(+)-adenosinetriphosphatase) confirmed this difference. To determine the source of this difference, sodium pump density was measured with the use of [3H]ouabain binding. Ectotherms and endotherms were found to share similar sodium pump numbers. Approximate densities (in pmol/g) were 250 for skeletal muscle, 500 for liver, 900 for heart, and 8,000 for kidney and brain. Therefore, differences in sodium pump activity between endotherms and ectotherms were due to differences in turnover rates or molecular activities of sodium pumps. Molecular activities of sodium pumps (in ATP/min) of tissues from endotherms were between 6,000 and 12,000 and, for ectotherms, between 1,500 and 2,500. Exceptions were found that included the heart of Bufo marinus. In a single invertebrate species studied, Charax destructor, the sodium pumps of the heart had a low molecular activity characteristic of ectothermic tissues. These results suggest that during the evolution of endothermy there was a general increase in the molecular activity of the sodium pump.

Download Full-text

Stimulation of Na+ , K+ -pump activity in skeletal muscle by methylxanthines: evidence and proposed mechanisms

Acta Physiologica Scandinavica ◽

10.1046/j.1365-201x.1996.200000.x ◽

1996 ◽

Vol 156 (3) ◽

pp. 347-353 ◽

Cited By ~ 21

Author(s):

M. I. LINDINGER ◽

R. G. WILLMETS ◽

T. J. HAWKE

Keyword(s):

Skeletal Muscle ◽

Pump Activity ◽

Stimulation Of

Download Full-text

Factors affecting membrane permeability and ionic homeostasis in the cold-submerged frog

Journal of Experimental Biology ◽

10.1242/jeb.203.2.405 ◽

2000 ◽

Vol 203 (2) ◽

pp. 405-414 ◽

Cited By ~ 6

Author(s):

P.H. Donohoe ◽

T.G. West ◽

R.G. Boutilier

Keyword(s):

Skeletal Muscle ◽

Membrane Potential ◽

Membrane Permeability ◽

Rana Temporaria ◽

Ion Homeostasis ◽

Resting Membrane Potential ◽

Tissue Water ◽

Factors Affecting ◽

Ion Gradients ◽

Pump Activity

Frogs (Rana temporaria) were submerged at 3 degrees C in either normoxic (P(O2)=155 mmHg, P(O2)=20 kPa) or hypoxic (P(O2)=60 mmHg; P(O2)=8 kPa) water for up to 16 weeks, and denied air access, to mimic the conditions of an ice-covered pond during the winter. The activity of the skeletal muscle Na(+)/K(+) pump over the first 2 months of hibernation, measured by ouabain-inhibitable (22)Na(+) efflux, was reduced by 30 % during normoxia and by up to 50 % during hypoxia. The reduction in Na(+)/K(+) pump activity was accompanied by reductions in passive (22)Na(+) influx and (86)Rb(+) efflux (effectively K(+) efflux) across the sarcolemma. This may be due to a decreased Na(+) permeability of the sarcolemma and a 75 % reduction in K(+) leak mediated by ATP-sensitive K(+) channels (‘K(ATP)’ channels). The lowered rates of (22)Na(+) and (86)Rb(+) flux are coincident with lowered transmembrane ion gradients for [Na(+)] and [K(+)], which may also lower Na(+)/K(+) pump activity. The dilution of extracellular [Na(+)] and intracellular [K(+)] may be partially explained by increased water retention by the whole animal, although measurements of skeletal muscle fluid compartments using (3)H-labelled inulin suggested that the reduced ion gradients represented a new steady state for skeletal muscle. Conversely, intracellular ion homeostasis within ventricular muscle was maintained at pre-submergence levels, despite a significant increase in tissue water content, with the exception of the hypoxic frogs following 4 months of submergence. Both ventricular muscles and skeletal muscles maintained resting membrane potential at pre-submergence levels throughout the entire period of hibernation. The ability of the skeletal muscle to maintain its resting membrane potential, coincident with decreased Na(+)/K(+) pump activity and lowered membrane permeability, provided evidence of functional channel arrest as an energy-sparing strategy during hibernation in the cold-submerged frog.

Download Full-text

Faculty Opinions recommendation of Skeletal muscle signaling and the heart rate and blood pressure response to exercise: insight from heart rate pacing during exercise with a trained and a deconditioned muscle group.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717988741.793487891 ◽

2013 ◽

Author(s):

William Sheel

Keyword(s):

Blood Pressure ◽

Skeletal Muscle ◽

Heart Rate ◽

Blood Pressure Response ◽

Pressure Response ◽

Muscle Group ◽

Response To Exercise

Download Full-text

The dual nature of the membrane potential increase associated with the activity of the sodium/potassium exchange pump in skeletal muscle fibres

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1977.0110 ◽

1977 ◽

Vol 198 (1133) ◽

pp. 463-472 ◽

Cited By ~ 5

Keyword(s):

Skeletal Muscle ◽

Membrane Potential ◽

Muscle Fibres ◽

Potassium Depletion ◽

Sodium Potassium ◽

Dual Nature ◽

Tubular System ◽

Pump Activity ◽

Skeletal Muscle Fibres ◽

Potassium Exchange

Results are presented which suggest that the contribution to the membrane potential in frog skeletal muscle evoked by ionic pump activity is made up of two components. One of these is directly related to the ‘electrogenic’ mode of pump action; the other, of similar magnitude, is an indirect effect due to potassium depletion in the lumen of the T -tubular system. The extent of this depletion has been estimated.

Download Full-text