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Biomedical subjects

T Clausen

Publications and source records attributed to T Clausen.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effects of potassium deficiency on growth and protein synthesis in skeletal muscle and the heart of rats.

The effects of potassium deficiency on growth, K content and protein synthesis have been compared in 4-13-week-old rats. When maintained on K-deficient fodder (1 mmol/kg) rats ceased to grow within a few days, and the incorporation of [3H]leucine into skeletal muscle protein in vivo was reduced by 28-38%. Pair-feeding experiments showed that this inhibition was not due to reduced energy intake. Following 14 d on K-deficient fodder, there was a further reduction (39-56%) in the incorporation of [3H]leucine into skeletal muscle protein, whereas the incorporation into plasma, heart and liver proteins was not affected. The accumulation of the non-metabolized amino acid alpha-aminoisobutyric acid in the heart and skeletal muscles was not reduced. The inhibitory effect of K deficiency on 3H-labelling of muscle protein was seen following intraperitoneal (10-240 min) as well as intravenous (10 min) injection of [3H]leucine. In addition, the incorporation of [3H]phenylalanine into skeletal muscle protein was reduced in K-depleted animals. Following acute K repletion in vivo leading to complete normalization of muscle K content, the incorporation of [3H]leucine into muscle protein showed no increase within 2 h, but reached 76 and 104% of the control level within 24 and 72 h respectively. This was associated with a rapid initial weight gain, but normal body-weight was not reached until after 7 weeks of K repletion. Following 7 d on K-deficient fodder the inhibition of growth and protein synthesis was closely correlated with the K content of the fodder (1-40 mmol/kg) and significant already at modest reductions in muscle K content. In vitro experiments with soleus muscle showed a linear relationship between the incorporation of [3H]leucine into muscle protein and K content, but the sensitivity to cellular K deficiency induced in vitro was much less pronounced than that induced in vivo. Thus, in soleus and extensor digitorum longus (EDL) muscles prepared from K-deficient rats, the incorporation of [3H]leucine was reduced by 30 and 47% respectively. This defect was completely restored by 24 h K repletion in vivo. It is concluded that in the intact organism protein synthesis and growth are very sensitive to dietary K deficiency and that this can only partly be accounted for by the reduction in cellular K content per se. The observations emphasize the need for adequate K supplies to ensure optimum utilization of food elements for protein synthesis and growth.

Animals↗
PubMed1989

Increased total concentration of Na-K pumps in vastus lateralis muscle of old trained human subjects.

The concentration of Na-K pumps was measured as the total capacity for [3H]ouabain binding in needle biopsies of the vastus lateralis muscle. Samples were obtained from young (28 +/- 0.2 yr) and old (68 +/- 0.6 yr) untrained control subjects and from groups of age-matched old trained subjects, who had been performing well-defined training programs at regular intervals for 12-17 yr. Measurements of maximum isometric force in knee extension showed that running and, especially, strength training produced a significant increase, whereas swim training was without effect. Both running and swim training increased endurance of knee extension, whereas strength training had a negative effect. When compared with untrained age-matched subjects, the swim-, running-, and strength-trained subjects demonstrated increased concentration of [3H]ouabain binding sites of 30% (P less than 0.01), 32% (P less than 0.05), and 40% (P less than 0.05), respectively. In the entire group of 28 individuals tested, maximum isometric strength and the concentration of [3H]ouabain binding sites showed correlation (r = 0.49, P less than 0.01). This upregulation of Na-K pump concentration might contribute to the reduction in exercise-induced hyperkalemia seen in trained subjects.

Adult↗
PubMed1988

Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics.

Animal studies have shown that potassium depletion induced by diuretics or potassium deficient fodder leads to a selective decrease in the concentrations of potassium and in the concentration of sodium-potassium pumps in skeletal muscle. In 25 patients who had received diuretics for 2-14 years the mean concentrations of potassium, magnesium, and sodium-potassium pumps were measured in skeletal muscle biopsy specimens and were significantly lower than in those from a group of age matched controls. The reductions in all three variables were significant in those patients receiving diuretics for arterial hypertension as well as in those being treated for congestive heart failure. In 14 patients the mean muscle potassium concentration was below the control range, but only one of those was hypokalaemic (3.4 mmol/l), and 13 were receiving potassium supplements. In 15 patients the mean muscle magnesium concentration was below normal, and the mean muscle potassium and magnesium concentrations showed a linear correlation. In 12 patients in whom the mean muscle potassium concentration was below 80 mumol/g wet weight there was a linear correlation between the cellular potassium:sodium ratio and the concentration of 3H-ouabain binding sites indicating that potassium deficiency also leads to a down regulation of sodium-potassium pumps in human skeletal muscle. In spite of potassium supplements long term treatment with diuretics may lead to potassium and magnesium deficiencies, which are not detectable using the standard methods of serum analysis. The changes in concentrations of electrolytes and sodium-potassium pumps associated with treatment with diuretics may impair muscle function and potassium homoeostasis and interfere with the distribution of digitalis glycosides.

Adult↗
PubMed1988

A simple and rapid method for the determination of the concentrations of magnesium, sodium, potassium and sodium, potassium pumps in human skeletal muscle.

1. For the diagnosis of electrolyte disorders, data on skeletal muscle composition are often valuable, but rarely available. We have therefore developed a simple and rapid needle biopsy procedure for the determination of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in muscle. 2. Using a Bergström needle, biopsies weighing around 25 mg were taken from the vastus lateralis muscle of 18 normal subjects (aged 44-86 years) and extracted with trichloroacetic acid (TCA). The concentrations of K+, Na+ and Mg2+ were 90.7 +/- 1.8, 31.9 +/- 1.6 and 9.5 +/- 0.2 mumol/g wet wt., respectively (means +/- SE). 3. The TCA extraction gave the same values as digestion with 65% HNO3 or 35% H2O2, could be used over the weight range 10-55 mg and showed a Mg2+ recovery of 101.7%. 4. The concentration of Na+, K+-pumps was quantified as the total capacity for [3H]ouabain binding. In vastus lateralis biopsies obtained from six normal subjects the mean value was 258 +/- 16 pmol/g wet wt. 5. Comparison of the concentrations of K+, Mg2+ and [3H]ouabain-binding sites in samples obtained post mortem showed modest variation among different muscles with varying fibre composition. 6. Measurements of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in duplicate biopsies of the vastus lateralis yield values which seen representative for the total pool of skeletal muscle fibres and can be performed within a few hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Effects of adrenaline on excitation-induced stimulation of the sodium-potassium pump in rat skeletal muscle.

Experiments were performed on isolated rat soleus and extensor digitorum longus (EDL) muscles of 4-week-old rats. In the soleus, direct electrical stimulation for 10 min induced a frequency-dependent increase in the ouabain-suppressible 86Rb+ uptake, which was maximal (+110%) at a frequency of 2 Hz. In the EDL this frequency only induced a 31% increase. A supramaximal concentration of adrenaline (10 mumol l-1) stimulated ouabain-suppressible 86Rb+ uptake by 80% and 27% in soleus and EDL, respectively. The combined effect of stimulation at 2 Hz and adrenaline was not significantly larger than each of the interventions alone in either of the muscles. The fractional loss of 22Na+ from soleus muscle was increased by around 50% by the exposure to adrenaline, electrical stimulation at 2 Hz or a combination of both. The effect of electrical stimulation on 22Na+ efflux was not prevented by addition of propranolol (1 or 10 mumol l-1). The results indicate that the stimulation of active Na+-K+ transport induced by adrenaline or electrical stimulation is much more pronounced in soleus (slow-twitch) muscle than in EDL (fast-twitch) muscle. Since it has been suggested that an accumulation of K+ ions in the extracellular space may play a role in the development of fatigue (Bigland-Ritchie 1984), our findings might be related to the fact that slow-twitch muscles have a much higher resistance to fatigue than fast-twitch muscles (Burke et al. 1971).

Action Potentials↗
PubMed1988

Quantitative determination of Na+-K+-ATPase and other sarcolemmal components in muscle cells.

A recurring problem in the characterization of plasma membrane enzymes in tissues and cells is whether the samples tested are representative for the entire population of enzyme molecules present in the starting material. Measurements of [3H]-ouabain binding, enzyme activity, and maximum transport capacity all indicate that the concentration of Na+-K+ pumps in mammalian skeletal muscle is high (300-800 pmol/g wet wt). Studies on Na+-K+-ATPase activity in isolated sarcolemma, however, generally give little or no information on total cellular enzyme concentration. Due to the low and variable enzyme recovery (0.2-8.9%), such subcellular preparations may, therefore, give misleading data on factors regulating Na+-K+-ATPase in heart and skeletal muscle cells. As the same isolation and purification procedures are used for the study of other sarcolemmal components (lipids, hormone receptors, enzymes, and other transport systems), this inadequate recovery has general implications for statements on regulatory changes in the sarcolemmal composition of muscle cells. On the other hand, complete quantification of Na+-K+-ATPase in muscle tissue can now be achieved using simple procedures and the entire material (intact muscle fibers, biopsies, and whole homogenates). Recent studies have shown that regulatory changes in the entire population of Na+-K+ pumps in muscle can be quantified in measurements of [3H]-ouabain binding, K+-activated 3-O-methylfluorescein phosphatase activity, as well as maximum ouabain suppressible Na+-K+ transport capacity.

Animals↗
PubMed1988

Effects of thyroid hormone on Na+-K+ transport in resting and stimulated rat skeletal muscle.

The effects of hypothyroidism and 3,5,3'-triiodothyronine (T3) treatment on passive Na+-K+ fluxes and Na+-K+ pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T3 (20 micrograms/100 g body wt), K+ efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na+ influx but no significant increase in [3H]ouabain binding site concentration. After 3 days of T3 treatment, the stimulating effect on K+ efflux and Na+ influx in soleus reached a plateau approximately 80 and 40% above control levels, respectively, whereas the maximum increase in [3H]ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased 86Rb efflux by 30%. The efflux of K+ and the influx of Na+ per contraction (both approximately 7 nmol/g wet wt) as well as the net loss of K+ induced by electrical stimulation were unaffected by T3 treatment. The rise in resting K+ efflux after 12-24 h of T3 treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca2+ concentration may contribute to the early rise in K+ efflux. It is concluded that the early rise in the resting passive leaks of Na+ and K+ induced by T3 is a major driving force for Na+-K+ pump synthesis.

Animals↗
PubMed1987

Inadequate supplies of potassium and magnesium in relief food--implications and countermeasures.

Analyses of relief food used in Ethiopia showed that, because of food refinement, 6 out of 10 samples of cereals contained too little potassium and magnesium to cover daily needs. Malnutrition is often associated with gastrointestinal infections, which lead to further deficiency of these electrolytes. Potassium and magnesium are required for protein synthesis, growth, and tissue repair. Since protein supplies are often marginal, relief food should contain sufficient potassium and magnesium to allow optimum utilisation of dietary nitrogen sources. This may be achieved by using coarse qualities of cereals, by supplementing cereals with legumes, and by avoiding cooking procedures that extract these salts from the cereals.

Disasters↗
PubMed1987

Quantification of the maximum capacity for active sodium-potassium transport in rat skeletal muscle.

1. Intact skeletal muscle fibres have been shown to contain a high concentration of [3H]ouabain binding sites (100-800 pmol g wet wt.-1). Under resting conditions, however, it seems that in isolated muscles only 2-6% of the corresponding expected capacity for active Na+-K+ transport is utilized. 2. In order to determine whether all [3H]ouabain binding sites in rat soleus muscle represent functional Na+-K+ pumps, we have measured the maximum rates of the ouabain-suppressible components of isotopic fluxes of Na+ and K+ as well as the net changes in Na+-K+ contents. 3. Experiments with soleus muscles isolated from 4-week-old rats showed that following Na+ loading (I.C. Na+, 126 mmol l-1), the ouabain-suppressible 86Rb+ uptake and 22Na+ efflux as measured during 3 min of exposure to K+-rich buffer were 5800 and 6500 nmol g wet wt.-1 min-1, respectively. 4. These initial high rates of isotopic fluxes were confirmed by flame photometric measurements of Na+-K+ contents. The ouabain-suppressible 86Rb+ uptake had a temperature coefficient of 2.1, was inhibited by 2,4-dinitrophenol, but showed no response to tetracaine, BaCl2, Ca2+-free buffer or tetraethylammonium chloride. 5. In soleus muscles, where the total population of [3H]ouabain binding sites had undergone changes as a result of differentiation, K+ depletion or pre-treatment with thyroid hormone, there was a significant correlation (r = 0.95, P less than 0.005) between the concentration of [3H]ouabain binding sites (260-1170 pmol g wet wt.-1) and the maximum ouabain-suppressible 86Rb+ uptake (2300-10,900 nmol g wet wt.-1 min-1). 6. It is concluded that by the combination of Na+ loading and high extracellular K+, the available Na+-K+ pumps as quantified by the [3H]ouabain binding capacity can be activated to reach a transport rate around 90% of the theoretical maximum at 30 degrees C.

2,4-Dinitrophenol↗
PubMed1987

Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle.

To identify possible cause-effect relationships between changes in active Na+-K+ transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in sugar transport. Ouabain, at a concentration (10(-3) M) sufficient to block active Na+-K+ transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na+ loading in K+-free buffer, the return to K+-containing standard buffer caused marked stimulation of active Na+-K+ transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the Na+-K+ pump leads to decreased intracellular Na+ concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na+-K+ transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na+ influx via the Na+/H+-exchange system.

3-O-Methylglucose↗
PubMed1986

Training increases the concentration of [3H]ouabain-binding sites in rat skeletal muscle.

Exercise is associated with a net loss of K+ from the working muscles and an increased plasma K+ concentration, indicating that the capacity for intracellular reaccumulation of K+ is exceeded. Training reduces the exercise-induced rise in plasma K+, and an increased plasma [K+] may interfere with physical performance. Since the clearing of K+ from the extracellular space depends on the capacity for active K+ uptake in skeletal muscle, the effects of training and inactivity on the total concentration of (Na+ + K+)-ATPase was determined. Following 6 weeks of swim training, the concentration of [3H]ouabain-binding sites in rat hindlimb muscles was up to 46% (P less than 0.001) higher than in those obtained from age-matched controls. Whereas muscle Na+, K+ contents remained unchanged, the concentration of citrate synthase increased by up to 76% (P less than 0.001). Training induced no change in the [3H]ouabain-binding-site concentration in the diaphragm, but in the heart ventricles, the K+-dependent 3-O-methylfluorescein phosphatase activity increased by 20% (P less than 0.001). Muscle inactivity induced by denervation, plaster immobilisation or tenotomy reduced the [3H]ouabain-binding-site concentration by 20-30% (P less than 0.02-0.001) within 1 week. In conclusion, training leads to a significant and reversible rise in the concentration of (Na+ + K+)-ATPase in muscle cells. This may be of importance for the beneficial effects on physical performance by improving the maximum capacity for K+ clearance.

Animals↗
PubMed1986

The effects of thyroid hormones on 3H-ouabain binding site concentration, Na,K-contents and 86Rb-efflux in rat skeletal muscle.

Using a recently developed method based upon vanadate facilitated 3H-ouabain binding, the total concentration of 3H-ouabain binding sites was determined in biopsies of rat skeletal muscles containing varying proportions of slow-twitch fibres. In extensor digitorum longus, diaphragm, gastrocnemius and soleus muscles from mature (12-week-old) hyperthyroid rats the values obtained were respectively 2.6, 3.5, 5.1 and 9.8 times higher than those found in the same muscles from hypothyroid animals. This indicates that the effect of thyroid hormones is more pronounced on slow-twitch than on fast-twitch fibres. The changes in 3H-ouabain binding site concentration with thyroid status could not be accounted for by differences in affinity or the rate of 3H-ouabain binding. In young (4-5 week old) rats, where the K-content and the 3H-ouabain binding site concentration in muscle had been reduced by K-depletion, T3-pretreatment produced an even larger relative increase in the 3H-ouabain binding site concentration than in age-matched controls, but no increase in K-content. Therefore, the downregulation of 3H-ouabain binding sites seen during K-depletion cannot be attributed to a decreased response to thyroid hormones. In normal rats the marked stimulating effect of thyroid hormone on the synthesis of 3H-ouabain binding sites was not associated with any significant change in K-content, but clearly preceded by a significant (P less than 0.001) rise in the efflux of 86Rb.

Animals↗
PubMed1986

Effects of semi-starvation and potassium deficiency on the concentration of [3H]ouabain-binding sites and sodium and potassium contents in rat skeletal muscle.

1. Using vanadate-facilitated [3H]ouabain binding, the effect of semi-starvation on the total concentration of [3H]ouabain-binding sites was determined in samples of rat skeletal muscle. When 12-week-old rats were semi-starved for 1, 2 or 3 weeks on one-third to half the normal daily energy intake, the [3H]ouabain-binding site concentration in soleus muscle was reduced by 19, 24 and 25% respectively. In extensor digitorum longus, diaphragm and gastrocnemius muscles the decrease after 2 weeks of semi-starvation was 15, 18 and 17% respectively. The decrease was fully reversible within 3 d of free access to the diet. Complete deprivation of food for 5 d caused a reduction of 25% in soleus muscle [3H]ouabain-binding-site concentration. It was excluded that the reduction in [3H]ouabain binding was due to a reduced affinity of the binding site for [3H]ouabain. 2. Semi-starvation of 12-week-old rats for 3 weeks caused a reduction of 45 and 53% in 3,5,3'-triiodothyronine (T3) and thyroxine (T4) levels respectively. As reduced thyroid hormone levels have previously been found to decrease [3H]ouabain-binding-site concentration in skeletal muscle, this points to the importance of T3 and T4 in the down-regulation of the [3H]ouabain-binding-site concentration in skeletal muscle with semi-starvation. Whereas potassium depletion caused a decrease in K content as well as in [3H]ouabain-binding-site concentration in skeletal muscles, semi-starvation caused only a tendency to a decrease in K content. Thus, K depletion is not a major cause of the reduction in [3H]ouabain-binding-site concentration with semi-starvation. 3. Due to its high concentration of Na,K pumps, skeletal muscle has a considerable capacity for clearing K from the plasma as well as for the binding of digitalis glycosides. Semi-starvation causes a severe reduction in the total skeletal muscle pool of Na,K pumps and may therefore be associated with impairment of K tolerance and increased digitalis toxicity.

Animals↗
PubMed1986

Quantification of the 3H-ouabain binding site concentration in human myocardium: a postmortem study.

The 3H-ouabain binding site concentration in the human myocardium was determined by measuring vanadate facilitated binding of 3H-ouabain to necropsy specimens of the left ventricle. The 3H-ouabain binding to samples weighing 4-6 mg was specific and saturable and appeared to take place to only one population of high affinity binding sites. After death the 3H-ouabain binding capacity degraded relatively slowly. From 6 to 24 h after death a mean decrease of 11% was seen in five patients, being significant in only one. In 15 patients aged 64-86 years the concentration of 3H-ouabain binding sites measured 6 h after death varied from 223 to 577 pmol X g-1 wet weight with no obvious relation to age or sex. The mean (SEM) value (413(26) pmol X g-1 wet weight) was 1.7 times higher than that previously reported for human myocardium. The concentrations of 3H-ouabain and 3H-digoxin binding sites were identical, and an excess of unlabelled ouabain completely prevented the specific binding of 3H-digoxin. In necropsy specimens weighing 1-2 mg from the endomyocardium obtained using a biotome the 3H-ouabain binding site concentration was in the same range as that in the myocardium. These findings indicate that it is possible to determine the concentration of Na, K-pumps in the human myocardium by measuring the 3H-ouabain binding capacity of biopsy specimens obtained during heart catheterisation or of specimens obtained within the first 18 h after death. This finding may be of importance for studying conditions in which the Na, K-pump concentration is suspected of undergoing variation.

Aged↗
PubMed1986

Effects of thyroid hormones on calcium contents and 45Ca exchange in rat skeletal muscle.

In 4-wk-old rats, pretreatment with L-triiodothyronine (T3) increased calcium content by 100% and the 30-min 45Ca uptake by 64% in the soleus, whereas the extensor digitorum longus (EDL) muscle showed no significant change. The stimulation of 45Ca uptake was resistant to dantrolene and methoxyverapamil (D600) and could not be attributed to altered permeability of the plasma membrane to calcium, but appears to reflect increased net accumulation of calcium in intracellular pools. The stimulating effect of high K0 (20 mM) on 45Ca uptake was more pronounced in soleus than in EDL and could be suppressed by dantrolene and D600. The results indicate that the effects of T3 on calcium content and 45Ca exchange are primarily exerted on muscles containing a large proportion of slow-twitch, oxidative fibers. In soleus muscle from hyperthyroid rats the stimulating effects of high K0 on 45Ca uptake and lactate production were, respectively, 3.4 and 4.5 times larger than in those obtained from controls. These observations further support the earlier proposed idea [C. van Hardeveld and T. Clausen. Am. J. Physiol. 247 (Endocrinol. Metab. 10): E421-E430, 1984] that the metabolic effects of thyroid hormone depend on the availability of cellular as well as extracellular calcium.

Animals↗