Biomedical subjects

E R Chin

Publications and source records attributed to E R Chin.

17 recordsLinked to original sources

PubMed2000

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type.

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained.

Animals↗

PubMed2000

Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle.

Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.

Animals↗

PubMed1998

The contribution of pH-dependent mechanisms to fatigue at different intensities in mammalian single muscle fibres.

1. The contribution of intracellular pH (pHi) to the failure of Ca2+ release and inhibition of contractile proteins observed during fatigue was assessed in single intact mouse muscle fibres at 22 C. Fatigue was induced by repeated tetani at intensities designed to induce different levels of intracellular acidosis. Force and either intracellular free Ca2+ concentration ([Ca2+]i; measured using indo-1) or pHi (measured using SNARF-1) were recorded in fibres fatigued at two different intensities. 2. Intensity was varied by the repetition rate of tetani and quantified by the duty cycle (the fraction of time when the muscle was tetanized). Stimulation at the low intensity (duty cycle approximately 0.1) reduced force to 30 % of initial values in 206 +/- 21 s (60 +/- 7 tetani); at the high intensity (duty cycle approximately 0.3) force was reduced to 30% in 42 +/- 7 s (43 +/- 7 tetani) (P < 0.05; n = 14). 3. When force was reduced to 30 % of initial values, tetanic [Ca2+]i had fallen from 648 +/- 87 to 336 +/- 64 nM (48% decrease) at the low intensity but had only fallen from 722 +/- 84 to 468 +/- 60 nM (35% decrease) at the higher intensity (P < 0.05 low vs. high intensity; n = 7). 4. Fatigue resulted in reductions in Ca2+ sensitivity of the contractile proteins which were greater at the high intensity (pre-fatigue [Ca2+]i required for 50 % of maximum force (Ca50) = 354 +/- 23 nM; post-fatigue Ca50 = 421 +/- 48 nM and 524 +/- 43 nM for low and high intensities, respectively). Reductions in maximum Ca2+-activated force (Fmax) were similar at the two intensities (pre-fatigue Fmax = 328 +/- 22 microN; post-fatigue Fmax = 271 +/- 20 and 265 +/- 19 microN for low and high intensities, respectively). 5. Resting pHi was 7.15 +/- 0.05. During fatigue at the low intensity, pHi was reduced by 0.12 +/- 0.02 pH units and at the high intensity pHi was reduced by 0.34 +/- 0.07 pH units (P < 0.05; n = 5). 6. Our results indicate that the more rapid fall in force at a high intensity is due to a reduction in Ca2+ sensitivity of the contractile proteins, probably related to the greater acidosis. Our data also indicate that the failure of Ca2+ release and reduced maximum Ca2+-activated force observed during fatigue are not due to reductions in intracellular pH.

Acidosis↗

PubMed1998

Mice without myoglobin.

Myoglobin, an intracellular haemoprotein expressed in the heart and oxidative skeletal myofibres of vertebrates, binds molecular oxygen and may facilitate oxygen transport from erythrocytes to mitochondria, thereby maintaining cellular respiration during periods of high physiological demand. Here we show, however, that mice without myoglobin, generated by gene-knockout technology, are fertile and exhibit normal exercise capacity and a normal ventilatory response to low oxygen levels (hypoxia). Heart and soleus muscles from these animals are depigmented, but function normally in standard assays of muscle performance in vitro across a range of work conditions and oxygen availability. These data show that myoglobin is not required to meet the metabolic requirements of pregnancy or exercise in a terrestrial mammal, and raise new questions about oxygen transport and metabolic regulation in working muscles.

Animals↗

PubMed1998

A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.

Slow- and fast-twitch myofibers of adult skeletal muscles express unique sets of muscle-specific genes, and these distinctive programs of gene expression are controlled by variations in motor neuron activity. It is well established that, as a consequence of more frequent neural stimulation, slow fibers maintain higher levels of intracellular free calcium than fast fibers, but the mechanisms by which calcium may function as a messenger linking nerve activity to changes in gene expression in skeletal muscle have been unknown. Here, fiber-type-specific gene expression in skeletal muscles is shown to be controlled by a signaling pathway that involves calcineurin, a cyclosporin-sensitive, calcium-regulated serine/threonine phosphatase. Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters. Conversely, inhibition of calcineurin activity by administration of cyclosporin A to intact animals promotes slow-to-fast fiber transformation. Transcriptional activation of slow-fiber-specific transcription appears to be mediated by a combinatorial mechanism involving proteins of the NFAT and MEF2 families. These results identify a molecular mechanism by which different patterns of motor nerve activity promote selective changes in gene expression to establish the specialized characteristics of slow and fast myofibers.

3T3 Cells↗

PubMed1997

Effects of reduced muscle glycogen concentration on force, Ca2+ release and contractile protein function in intact mouse skeletal muscle.

1. The purpose of this study was to examine the effects of reduced glycogen concentration on force, Ca2+ release and myofibrillar protein function during fatigue in skeletal muscle. Force and intracellular free Ca2+ concentration ([Ca2+]i) were measured in single mammalian skeletal muscle fibres during fatigue and recovery. Glycogen was measured in bundles of 20-40 fibres from the same muscle under the same conditions. 2. Fatigue was induced by repeated maximum tetani until force was reduced to 30% of initial. This was associated with a reduction in muscle glycogen to 27 +/- 6% of control values. In fibres allowed to recover for 60 min in the presence of 5.5 mM glucose (n = 6), tetanic (100 Hz) force recovered fully but tetanic [Ca2+]i remained at 82 +/- 8% of initial values. This prolonged depression in Ca2+ release was not associated with decreased muscle glycogen since glycogen had recovered to pre-fatigue levels (157 +/- 42%). 3. To examine the responses under conditions of reduced muscle glycogen concentration, fibres recovered from fatigue for 60 min in the absence of glucose (n = 6). After glucose-free recovery, the decreases in tetanic force and [Ca2+]i were only partially reversed (to 64 +/- 8% and 57 +/- 7% of initial values, respectively). These alterations were associated with a sustained reduction in muscle glycogen concentration (27 +/- 4% of initial values). 4. In another set of fibres, fatigue was followed by 50 Hz intermittent stimulation for 22.6 +/- 4 min. With this protocol, tetanic force and [Ca2+]i partially recovered to 76 +/- 9% and 55 +/- 6% of initial levels, respectively. These changes were associated with a recovery of muscle glycogen (to 85 +/- 10%). 5. During fatigue, Ca2+ sensitivity and maximum Ca(2+)-activated force (Fmax) were depressed but these alterations were fully reversed when muscle glycogen recovered. When glycogen did not recover, Ca2+ sensitivity remained depressed but Fmax partially recovered. The altered myofibrillar protein function is probably due to alterations in inorganic phosphate levels or other metabolites associated with reduced levels of muscle glycogen. 6. These data indicate that the reductions in force, Ca2+ release and contractile protein inhibition observed during fatigue are closely associated with reduced muscle glycogen concentration. These findings also suggest that the changes in Ca2+ release associated with fatigue and recovery have two components-one which is glycogen dependent and another which is independent of glycogen but depends on previous activity.

Animals↗

PubMed1997

Role of intracellular calcium and metabolites in low-frequency fatigue of mouse skeletal muscle.

We have examined the extent to which prolonged reductions in low-frequency force (i.e., low-frequency fatigue) result from increases in intracellular free Ca2+ concentration ([Ca2+]i) and alterations in muscle metabolites. Force and [Ca2+]i were measured in mammalian single muscle fibers in response to short, intermediate, and long series of tetani that elevated the [Ca2+]i-time integral to 5, 17, and 29 microM x s, respectively. Only the intermediate and long series resulted in prolonged (>60 x min) reductions in Ca2+ release and low-frequency fatigue. When fibers recovered from the long series of tetani without glucose, Ca2+ release was reduced to a greater extent and force was reduced at high and low frequencies. These findings indicate that the decrease in sarcoplasmic reticulum Ca2+ release associated with fatigue has at least two components: 1) a metabolic component, which, in the presence of glucose, recovers within 1 h, and 2) a component dependent on the elevation of the [Ca2+]i-time integral, which recovers more slowly. It is this Ca2+-dependent component that is primarily responsible for low-frequency fatigue.

Animals↗

PubMed1997

Distribution of lactate and other ions in inactive skeletal muscle: influence of hyperkalemic lactacidosis.

The purpose of this study was to quantify changes in intracellular ion and acid-base status resulting from the net flux of ions between perfusate and noncontracting muscle of differing fibre type in response to a perfusate that simulated the ionic conditions seen during intense exercise. Isolated rat hind limbs were perfused for 80 min with a bovine erythrocyte perfusate. Two series of experiments were performed: a normal perfusate (NP, n = 8) or a lactacidotic perfusate (LP, n = 8) that simulated arterial plasma and blood composition during intense exercise ([Lac-] = 11.0 mequiv. L-1, [K+] = 7.5 mequiv. L-1, and nonvolatile acid concentration = 71 nequiv.L-1). Net ion fluxes were determined by the arteriovenous difference across the hind limb and perfusate flow. Muscle ion concentrations were measured in the soleus (SOL), plantaris (PLT), and white gastrocnemius (WG) muscles. In the NP group, small net effluxes of K+ and Lac- from muscle were observed, but there was no net flux of Na+ or CI-. During LP, an initial rapid net influx of Lac- into muscle (151.2 +/- 9.4 mu equiv. min-1. 100 g-1 at 5 min) was followed by a steady-state net influx of 24-37 mu equiv. min-1. 100 g-1 between 20 and 60 min. During LP, net influx of Na+, CI-, and K+ was greater than during NP and average 58.0 +/- 11.2, 30.0 +/- 7.5, and 7.5 +/- 1.9 mu equiv. min-1. 100 g-1, respectively. Following LP, muscle content of Na+ (WG only) and Lac- (WG, PLT, and SOL) was increased to a greater extent than following NP. The increased [Lac-]i contributed to an elevated [H+]i only in the slow oxidative SOL, consistent with the higher concentration of Lac- transporters, lower capacity to bind protons, and better regulation of [Na+]i in slow oxidative muscles. Calculated membrane potential (Em) was unchanged with NP but decreased on average from -76.2 +/- 1.2 to 63.4 +/- 2.2 mV with LP perfusion, with no difference among fibre types. The steady-state distribution of Lac- across the sarcolemma appears to be a function of both metabolic and transport processes; specifically, Lac- distribution was not fully explained by the membrane potential nor by the nonionic distribution of HLac as determined by the transmembrane pH gradient. It is concluded that inactive skeletal muscle modifies the ionic composition of blood perfusing the muscles. However, the altered ionic composition of these muscles may compromise their function as a result of an altered membrane potential in fast and slow muscles and increased [H+]i in slow oxidative muscles.

Acidosis, Lactic↗

PubMed1996

The role of elevations in intracellular [Ca2+] in the development of low frequency fatigue in mouse single muscle fibres.

1. Intracellular free calcium concentration ([Ca2+]i) and force were measured in isolated single skeletal muscle fibres from mice. The aim was to determine the extent to which elevations in [Ca2+]i during various stimulation protocols affected subsequent muscle performance. 2. A protocol of repeated tetanic stimulation which elevated [Ca2+]i and caused a large decline in force (fatigue) had a [Ca2+]-time integral of 36.4 +/- 8.1 microM s. A protocol of repeated tetani at a lower duty cycle (stimulation) caused only a small decline in force (9-16%) but elevated the [Ca2+]-time integral to 16.7 +/- 2.8 and 24.9 +/- 1.6 microM s in the absence and presence of 10 mM caffeine, respectively. Caffeine alone raised the [Ca2+]-time integral to 20.3 +/- 3.4 microM s. 3. Following the fatigue protocol there was a proportionately greater loss of force at low stimulation frequencies (30 and 50 Hz) compared with high frequencies (100 Hz) which persisted for up to an hour. This pattern of force loss could be attributed to a uniform reduction in [Ca2+]i at all frequencies. Similar effects were observed after elevating [Ca2+]i with the caffeine + stimulation protocol but were not observed after stimulation or caffeine alone. The higher [Ca2+]-time integrals during the fatigue and caffeine + stimulation protocols suggest that some threshold for [Ca2+]i must be reached before these effects are observed. 4. The reductions in low frequency force induced by the fatigue and caffeine + stimulation protocols were not due to decreased Ca2+ sensitivity or to decreases in maximum force-generating capacity of the contractile proteins and therefore are due to a failure of Ca2+ release. 5. The Ca(2+)-activated neutral protease (calpain) inhibitor calpeptin was not effective in preventing the effects of caffeine + stimulation indicating that the reduction in Ca2+ release was not due to calpain-mediated hydrolysis of the Ca2+ release channel. 6. Our findings indicate that low frequency fatigue results from increases in [Ca2+]i during fatigue and that these elevations in [Ca2+]i activate some process which leads to failure of excitation-contraction (E-C) coupling and Ca2+ release.

Animals↗

PubMed1996

Effects of tissue fractionation on exercise-induced alterations in SR function in rat gastrocnemius muscle.

Because studies into exercise-induced alterations in sarcoplasmic reticulum (SR) Ca2+ sequestration have produced conflicting reports, we have hypothesized that the differences in SR Ca(2+)-adenosinetriphosphatase (ATPase) activity and Ca2+ uptake in SR fractions observed in different studies are due to different SR isolation techniques. To investigate this possibility, rat white and red gastrocnemius muscles from control and run animals were studied by using two conventional isolation techniques to obtain a crude microsomal fraction and an isolated SR vesicle (SRV) fraction. Indexes of CM and SRV function were compared with measurements from whole muscle homogenate. Treadmill running to exhaustion did not alter SR protein yields, percent SR extraction, or basal or Ca(2+)-ATPase purification in either fraction. Ca(2+)-activated ATPase activity was not altered by exercise in any of the fractions examined, but Ca2+ uptake was reduced in the homogenates (9.48 +/- 1.4 to 6.90 +/- 0.8 nmol . mg-1.min-1) and SRV fractions (84.0 +/- 11.5 to 50.7 +/- 14.0 nmol . mg-1.min-1) from the red gastrocnemius at free Ca2+ concentrations of 600-700 nM. These data indicate that reductions in SR Ca2+ uptake are dissociated from changes in Ca(2+)-ATPase in vitro and occur only in a specific population of vesicles. The mechanisms underlying these alterations are not known but may involve a reduction in the number of Ca(2+)-ATPase enzymes or a selective sedimentation of damaged vesicles in the SRV fraction.

Adenosine Triphosphatases↗

PubMed1995

Failure of short term stimulation to reduce sarcoplasmic reticulum Ca(2+)-ATPase function in homogenates of rat gastrocnemius.

To examine the effect of short term intense activity on sarcoplasmic reticulum (SR) Ca2+ sequestering function, the gastrocnemius (G) muscles of 11 anaesthetized male rats (weight, 411 +/- 8 g, X +/- SE) were activated using supramaximal, intermittent stimulation (one train of 0.2 msec impulses per sec of 100 msec at 100 Hz). Homogenates were obtained from stimulated white (WG-S) and red (RG-S) tissues, assayed for Ca2+ uptake and maximal Ca2+ ATPase activity and compared to contralateral controls (WG-C, RG-C). Calcium uptake (nmoles/mg protein/min) determined using Indo-1 and at [Ca2+]i concentrations between 300-400 nM was unaffected (p > 0.05) by activity in both WG (6.14 + 0.43 vs 5.37 + 0.43) and RG (3.21 + 0.18 vs 3.07 + 0.20). Similarly, no effect (p > 0.05) of contractile activity was found for maximal Ca2+ ATPase activity (mumole/mg protein/min) determined spectrophotometrically in RG (0.276 + 0.03 vs 0.278 + 0.02). In WG, Ca2+ ATPase activity was 15% higher in WG-S compared to WG-C (0.412 + 0.03 vs 0.385 + 0.04). Repetitive stimulation resulted in a reduction in tetanic tension of 74% (p < 0.05) by 2 min in the G muscle. By the end of the stimulation period, ATP concentration was reduced (p < 0.05) by 57% in the WG and by 47% in the RG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1995

Effects of prolonged low frequency stimulation on skeletal muscle sarcoplasmic reticulum.

The role of prolonged electrical stimulation on sarcoplasmic reticulum (SR) Ca2+ sequestration measured in vitro and muscle energy status in fast white and red skeletal muscle was investigated. Fatigue was induced by 90 min intermittent 10-Hz stimulation of rat gastrocnemius muscle, which led to reductions (p < 0.05) in ATP, creatine phosphate, and glycogen of 16, 55, and 49%, respectively, compared with non-stimulated muscle. Stimulation also resulted in increases (p < 0.05) in muscle lactate, creatine, Pi, total ADP, total AMP, IMP, and inosine. Calculated free ADP (ADPf) and free AMP (AMPf) were elevated 3- and 15-fold, respectively. No differences were found in the metabolic response between tissues obtained from the white (WG) and red (RG) regions of the gastrocnemius. No significant reductions is SR Ca2+ ATPase activity were observed in homogenate (HOM) or a crude SR fraction (CM) from WG or RG muscle following exercise. Maximum Ca2+ uptake in HOM and CM preparations was similar in control (C) and stimulated (St) muscles. However, Ca2+ uptake at 400 nM free Ca2+ was significantly reduced in CM from RG (0.108 +/- 0.04 to 0.076 +/- 0.02 mumol.mg-1 protein.min-1 in RG - C and RG - St, respectively). Collectively, these data suggest that reductions in muscle energy status are dissociated from changes in SR Ca2+ ATPase activity in vitro but are related to Ca2+ uptake at physiological free [Ca2+ bd in fractionated SR from highly oxidative muscle. Dissociation of SR Ca2+ ATPase activity from Ca2+ uptake may reflect differences in the mechanisms evaluated by these techniques.

Animals↗

PubMed1994

Technical considerations for assessing alterations in skeletal muscle sarcoplasmic reticulum Ca(++)-sequestration function in vitro.

A multiple measurement system for assessing sarcoplasmic reticulum (SR) Ca(++)-ATPase activity and Ca(++)-uptake was used to examine the effects of SR fractionation and quick freezing on rat white (WG) and red (RG) gastrocnemius muscle. In vitro measurements were performed on whole muscle homogenates (HOM) and crude microsomal fractions (CM) enriched in SR vesicles before and after quick freezing in liquid nitrogen. Isolation of the CM fraction resulted in protein yields of 0.96 +/- 0.1 and 0.99 +/- 0.1 mg/g in WG and RG, respectively. The percent Ca(++)-ATPase recovery for CM compared to HOM was 14.5% (WG) and 10.1% (RG). SR Ca(++)-activated Ca(++)-ATPase activity was not affected by quick freezing of HOM or CM, but basal ATPase was reduced (P < 0.05) in frozen HOM (5.12 +/- 0.18-3.98 +/- 0.20 mole/g tissue/min in WG and from 5.39 +/- 0.20-4.48 +/- 0.24 mumole/g tissue/min in RG). Ca(++)-uptake was measured at a range of physiological free [Ca++] using the Ca++ fluorescent dye Indo-1. Maximum Ca(++)-uptake rates when corrected for initial [Ca++]f were not altered in HOM or CM by quick freezing but uptake between 300 and 400nM free Ca++ was reduced (P < 0.05) in quick frozen HOM (1.30 +/- 0.1-0.66 +/- 0.1 mumole/g tissue/min in WG and 1.04 +/- 0.2-0.60 +/- 0.1 mumole/g tissue/min in RG). Linear correlations between Ca(++)-uptake and Ca(++)-ATPase activity measured in the presence of the Ca++ ionophore A23187 were r = +0.25, (P < 0.05) and r = +0.74 (P < 0.05) in HOM and CM preparations, respectively, and were not altered by freezing. The linear relationships between HOM and CM maximum Ca(++)-uptake (r = +0.44, P < 0.05) and between HOM and CM Ca(++)-ATPase activity (r = +0.34, P < 0.05) were also not altered by tissue freezing. These data suggest that alterations in maximal SR Ca(++)-uptake function and maximal Ca(++)-ATPase activity may be measured in both HOM and CM fractions following freezing and short term storage.

Animals↗

PubMed1993

Na(+)-K+ ATPase concentration in different adult rat skeletal muscles is related to oxidative potential.

To investigate the relationship among fibre type, oxidative potential, and Na(+)-K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259 +/- 8 g (mean +/- SE) were sacrificed and the soleus (SOL), extensor digitorum longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed. These muscles were chosen as being representative of the two major fibre type populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na(+)-K+ ATPase concentration (pmol.g-1 wet weight), measured by the [3H]ouabain binding technique, differed (p < 0.01) only between the WV (238 +/- 7.9) and the SOL (359 +/- 9.6), EDL (365 +/- 10), and RV (403 +/- 12). Similarly, muscle oxidative potential as measured by the maximal activity of citrate synthase was different (p < 0.01) only between the WV and the other three muscles. Citrate synthase activity (mumol.min-1.g-1 wet weight) was 4.0 +/- 0.7, 12.3 +/- 0.9, 9.1 +/- 0.7, and 11.3 +/- 1.0 in the WV, SOL, EDL, and RV, respectively. These results indicate that Na(+)-K+ ATPase concentration is not related to the speed of contraction but to the oxidative potential of the muscle. Since chronic activity is a primary determinant of oxidative potential, it would be expected that increases in Na(+)-K+ ATPase would accompany increases in muscle utilization.

Animals↗

PubMed1993

Increases in human skeletal muscle Na(+)-K(+)-ATPase concentration with short-term training.

To investigate the effect of short-term training on Na(+)-K(+)-adenosine triphosphatase (ATPase) concentration in skeletal muscle and on plasma K+ homeostasis during exercise, 9 subjects performed cycle exercise for 2 h per day for 6 consecutive days at 65% of maximal aerobic power (VO2 max). Na(+)-K(+)-ATPase concentration determined from biopsies obtained from the vastus lateralis muscle using the [3H]ouabain-binding technique increased 13.6% (P < 0.05) as a result of the training (339 +/- 16 vs. 385 +/- 19 pmol/g wet wt, means +/- SE). Increases in Na(+)-K(+)-ATPase concentration were accompanied by a small but significant increase in VO2 max (3.36 +/- 0.16 vs. 3.58 +/- 0.13 l/min). The increase in arterialized plasma K+ concentration and plasma K+ content determined during continuous exercise at three different intensities (60, 79, and 94% VO2 max) was depressed (P < 0.05) following training. These results indicate that not only is training capable of inducing an upregulation in sarcolemmal Na(+)-K(+)-ATPase concentration in humans, but provided that the exercise is of sufficient intensity and duration, the upregulation can occur within the first week of training. Moreover, our findings are consistent with the notion that the increase in Na(+)-K(+)-ATPase pump concentration attenuates the loss of K+ from the working muscle.

Adult↗

PubMed1992

Time-dependent increases in Na+,K(+)-ATPase content of low-frequency-stimulated rabbit muscle.

Chronic low-frequency stimulation of rabbit fast-twitch muscle induced time-dependent increases in the concentration of the sarcolemmal Na+,K(+)-ATPase and in mitochondrial citrate synthase activity. The almost twofold increase in Na+,K(+)-ATPase preceded the rise in citrate synthase and was complete after 10 days of stimulation. We suggest that the increase in Na+,K(+)-ATPase enhances resistance to fatigue of low-frequency-stimulated muscle prior to elevations in aerobic-oxidative capacity.

Animals↗

PubMed1991

Lactate metabolism in inactive skeletal muscle during lactacidosis.

Contributions of carbohydrate and fat metabolism to the removal of a lactate (Lac-) load were quantified in inactive soleus (SL), plantaris (PL), and white gastrocnemius (WG) rat hindlimb muscle. Male Sprague-Dawley rats were perfused for 60 min with normal perfusate (NP, n = 8) or a high-lactate perfusate (LP, n = 8), simulating ionic conditions found in arterial blood and plasma after intense exercise: Lac- = 11.0 mM, K+ = 7.88 mM, and pH = 7.15. Metabolite fluxes across the hindlimb were calculated from blood flow and arteriovenous differences. In NP, Lac- was continuously released (2.9 +/- 0.2 mumol.min-1 x 100 g-1). However, in LP, a rapid and significant uptake of Lac- increased muscle Lac- fivefold to 39.6 +/- 1.1, 33.1 +/- 2.2, and 28.8 +/- 1.7 mumol/g dry wt in SL, PL, and WG, respectively. Glucose and O2 uptakes were similar during LP and NP perfusion. Glycerol release increased eightfold to 3.3 +/- 0.7 mumol.min-1 x 100 g-1 in response to LP. Muscle ATP, creatine phosphate, glycogen, glycolytic intermediate, and triacylglycerol concentrations did not change. However, muscle lactate-to-pyruvate ratios were elevated in all muscles of the LP group postperfusion, indicating changes in the mass action ratio at the pyruvate dehydrogenase reaction. In LP, of 80 mumol of Lac- taken up, 11% was accounted for by increased muscle Lac-, 12-24% was oxidized, and 5% may have been involved in glycerol release. The remaining Lac- may have been involved in metabolic cycling along the glyconeogenic-glycolytic pathway and/or in triacylglycerol-free fatty acid substrate cycling.

Acidosis, Lactic↗