Effect of ATP concentration and pH on rigor tension development and dissociation of rigor complex in glycerinated rabbit psoas muscle fiber

Isometric rigor tension development of glycerinated rabbit psoas muscle fibers in a medium, due to the formation of rigor complexes, was estimated at varying ATP concentrations from 0 to 2.5 mM and pH values from 6.75 to 8.20. The dissociation of rigor complexes was also estimated under the same conditions. When muscle fibers developed rigor tension from the relaxed and rigor states, the magnitude of rigor tension increased with increasing concentration of ATP. Transition between rigor and relaxation in single fibers occurred discontinuously at constant levels (critical levels) of ATP which were determined by pH. The critical concentrations of ATP necessary for inducing the transitions between rigor and relaxed states were also increased exponentially with increased pH. Incomplete repetition of tension development by the same fiber was also observed. This incomplete reversibility was divided into two types: one which showed a decay in rigor tension and another which showed no decay. The reason for the incomplete reversibility was discussed.     

Spermidine cytotoxicity in vitro: Effect of serum and oxygen tension

Summary Plasma amine oxidase activities (benzylamine oxidase and spermine oxidase) were determined in the sera of a number of species of various ages. Benzylamine oxidase (BZO) activity, measured spectrophotometrically, was present in bovine, equine, and ovine species examined. Generally its activity in serum increased with the age of the animal. Spermine oxidase activity (SPO) was estimated by a bioassay of in vitro toxicity and did not necessarily correlate with BZO. Cytotoxicity in the presence of spermidine was found only in the sera of the ruminant species examined. Serum activity tended to rise with animal age; however, great variability was found in perinatal bovine sera. The 50% lethal dose (LD₅₀) of spermidine in the presence of 5% serum and 4×10⁴ NS₁ cells/ml was in the micromolar range. Aminoguanidine, a known inhibitor of SPO, could prevent the cytotoxic effects of exogenously added spermidine in vitro. In contrast, raising the ambient oxygen tension in the incubation environment to 95% lowered the LD₅₀ dose of spermidine required for cytotoxicity. The results suggest that a cell line of hematogenous origin is susceptible to the cytotoxic effects of the products of oxidative deamination of spermidine by SPO, an enzyme present in perinatal bovine sera, and that these cytotoxic effects are potentiated in the presence of an oxygen-enriched environment in vitro. This research was support in part by Grants AM 19899, AM 32237, and HD 00412 from the National Institute of Health, Bethesda, MD.     

Ultrastructure of a molluscan smooth muscle during phasic contractions and in the relaxed state

Tension and X-ray diffraction patterns are not always correlated in the smooth anterior retractor muscle (ABRM) of Mytilus edulis. The muscle produces equatorial intensity profiles of X-ray diffraction patterns corresponding to either a relaxed or a contracted structure. During phasic contractions, comprising a contracted as well a a relaxed phase, the diffracted intensity on the equator at 0.003 A^?1 changes within the first 10s after onset of stimulation. The tension reaches a maximum after about the same time. The time dependence of this intensity change during phasic contraction has been measured. It shows that the tension decays within 10s, but the relaxed structure needs 30–40 s to reestablish. There is no difference between the observed intensities from the tonic and phasic contracted states. Inactivated muscles with minimum tension, normally termed relaxed, can have either a “contracted” or a relaxed structure.     

Growth of aortic vascular smooth muscle cells in lowered oxygen tension

Summary Primary cultures of vascular smooth muscle cells, isolated from rat aorta, were grown under normoxic (20% O₂) and mildly hypoxic (5 % O₂) conditions. Cells from both conditions were compared for growth characteristics, morphology, protein synthesis, lysosomal enzyme activity, and oxygen consumption. In no case was a consistently significant difference observed. These observations indicate that these cells can adapt or are adapted to mildly hypoxic conditions. Moreover, these results may indicate that the culture of vascular smooth muscle cells in mild hypoxia represents a closer approximation of in vivo growth conditions for these cells.Supported by HL19242     

Stiffness and tension during and after sudden length changes of glycerinated rabbit psoas muscle fibres

A sudden stretch (within 0.3 ms) of glycerol-extracted rabbit psoas fibre bundle suspended in ATP-salt solution caused an immediate tension increase followed by a rapid tension decay (quick phase) which was nearly completed within 3 ms. The quick phase was missing or much reduced in the absence of ATP when the fibres were in rigor. Since the immediate stiffness of the fibres was nearly the same at the onset and at the end of the quick phase, the latter cannot be due to cross-bridges detachment per se. However, it may be ascribed to a conformational change (e.g. rotation) of attached bridges as suggested by Huxley and Simmons. Alternatively it might be explained by a slippage of attached cross-bridges. This mechanism would presuppose fast detachment and reattachment of strongly strained cross-bridges during the quick phase. Evidence for such a process was obtained by analysing the tension transients obtained when fibre bundles subjected to a large stretch were subsequently (within 10 ms) released to the initial length, as well as from stiffness measurements during the sudden length change: The stiffness was not found to be constant either during stretch or during the release. This may be taken to mean that the number of attached cross-bridges does not remain constant even during a rapid length change. In view of these results, the model proposed by Huxley and Simmons might be extended to take account of rapid attachment and detachment of crossbridges.     

Effect of posture on inspiratory muscle electromyogram response to hypercapnia

The aim of our study was to examine the effect of posture on inspiratory muscle activity response to hypercapnia. Recent research has revealed that in normal subjects the activation of the rib cage muscles and of the diaphragm is actually greater in the upright than in the supine position during resting tidal breathing. In this study we examined whether the upright position necessarily entails a greater activation of the inspiratory muscles also under conditions of ventilatory stress. For this purpose we compared the responses to CO2-rebreathing in the supine and sitting positions in five volunteers, by simultaneously recording the electromyogram of the diaphragm (EMGdi) and the intercostal muscles (EMGint). The electromyogram was recorded by means of surface electrodes to measure the EMG amplitude. While the slopes of ventilatory (VE) response to increasing arterial CO2 tension (PaCO2) were similar in the two positions, both the EMGdi-VE and EMGint-VE relationship showed steeper slopes in the supine than in the sitting position. In each CO2 run the increases in EMGdi were linearly related to those in EMGint. This relationship was not affected by the body position. These results suggested that, in spite of similar ventilatory responses to CO2-rebreathing in the lying and sitting positions, the supine position, in humans, required a higher activation of the inspiratory muscles.     

Serotonin modulates muscle function in the medicinal leech Hirudo verbana

The body wall muscles of sanguivorous leeches power mechanically diverse behaviours: suction feeding, crawling and swimming. These require longitudinal muscle to exert force over an extremely large length range, from 145 to 46 per cent of the mean segmental swimming length. Previous data, however, suggest that leech body wall muscle has limited capacity for force production when elongated. Serotonin (5-HT) alters the passive properties of the body wall and stimulates feeding. We hypothesized that 5-HT may also have a role in allowing force production in elongated muscle by changing the shape of the length-tension relationship (LTR). LTRs were measured from longitudinal muscle strips in vitro in physiological saline with and without the presence of 10 μM 5-HT. The LTR was much broader than previously measured for leech muscle. Rather than shifting the LTR, 5-HT reduced passive muscle tonus and increased active stress at all lengths. In addition to modulating leech behaviour and passive mechanical properties, 5-HT probably enhances muscle force and work production during locomotion and feeding.     

The timing of the electromyogram in the lateral myotomes of mackerel and saithe at different swimming speeds

Electromyogram (EMG) signals from two points at about 40% L and 65% L ( L = length) in the left latera1 muscle of mackerel ( Scomber scombrus L.) L = 28–33 cm a nd saithe ( Pollachius virens L.) L = 42–50 cm were recorded synchronously with films of steady straight swimming motions. In both species, the duration of EMG activity at both electrodes, remains a constant proportion of the tail cycle period Tat all the tail beat frequencies between 1–8 and 13 Hz. In mackerel and saithe respectively: onset of EMG activity at the front was 74% T and 77% T before the left-most tail blade position and fronl EMG-onset occurred 15% T and 18% T before rear onset. The duration of the EMG burst is longer at the front position (41% T and 47% T ) than at the rear (25% T and 27% T ), At all swimming speeds the wave of electrical activation of the muscle travelled between the two electrodes 25% L apart at a velocity between 1.5 and 1.6 L T ⁻¹. Frequencies of spikes within the burst of EMG activity rose from 30–40 Hz at 2 T s⁻¹ to 50–80 Hz at 8 T s⁻¹. In muscle at 40%L EMG-onset happens at phase 30° just after muscle strain at this point reaches its resting length while lengthening (360°). At 65% L EMG-onset occurs earlier in the strain cycle-350° just before the muscle reaches it resting length while lengthening (360°). This could represent within the length of the fish, a phase shift of up to 90° in the EMG-onset in relation to the muscle strain cycle. These timings are discussed in relation to optimized work output and a single instant of maximum bending moment all along the left side of the body.     

Okadaic acid uncouples myosin light chain phosphorylation and tension in smooth muscle

Tracheal smooth muscle precontracted with carbachol relaxes upon the addition of 3 μM okadaic add. Although cytosolic Ca²⁺ concentrations decrease, myosin light chain remains highly phosphorylated (50%). In smooth muscle treated with carbachol alone or carbachol plus okadaic acid ³²P is incorporated into a single peptide on myosin light chain which corresponds to the site phosphorylated by myosin light chain kinase. Treatment with okadaic acid alone does not result in myosin light chain phosphorylation or tension development. These results suggest that a cellular mechanism other than myosin light chain phosphorylation can regulate contractile tension.     

Interfacial tension of phosphatidylcholine-phosphatidylserine system in bilayer lipid membrane

The effect of pH of electrolyte solution on the interfacial tension of lipid membrane formed of phosphatidylcholine (PC, lecithin)–phosphatidylserine (PS) system was studied. In this article, three models describing the H⁺ and OH⁻ ions adsorption in the bilayer lipid surface are presented. In Model I and Model II, the surface is continuous with uniformly distributed functional groups constituting the centres of H⁺ and OH⁻ ions adsorption while in the other the surface is built of lipid molecules, free or with attached H⁺ and OH⁻ ions. In these models contribution of the individual lipid molecule forms to interfacial tension of the bilayer were assumed to be additive. In Model III the adsorption of the H⁺ and OH⁻ ions at the PC–PS bilayer surface was described in terms of the Gibbs isotherm. Theoretical equations are derived to describe this dependence in the whole pH range.     

Temperature and oxygen tension influence the development of muscle cellularity in embryonic rainbow trout

Muscle cellularity at a developmental stage around the time of hatching was examined in rainbow trout which had been reared from the eyed stage at three different temperature regimes (5, 10 and 15° C) and different O₂ tensions [70% of air saturation value (ASV) at 5° C, 100% of ASV at all temperatures, and 150% of ASV at 10 and 15° C]. It was found that, as has been shown for other species, there was a difference in muscle fibre numbers and fibre cross-sectional areas between some of the regimes. There was a decrease in fibre number at the intermediate and higher temperature, and a decrease in fibre size at the high temperature. The temperature effects observed were modified by the applied changes in O₂ tension. An increased O₂ tension at 10° C led to an increase in fibre size whereas a decrease in O₂ tension at the low temperature resulted in a decrease in fibre number. The largest total white muscle cross-sectional area was achieved at 10° C under high O₂ conditions. Temperature and O₂ tension therefore had a clear effect on muscle cellularity and there was a significant interaction between the two parameters.     

Supralinear and Supramodal Integration of Visual and Tactile Signals in Rats: Psychophysics and Neuronal Mechanisms

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Genetic analysis of psychiatric disorders in humans

Psychiatric disorders place a large burden not only on affected individuals and their families but also on societies and health services. Current treatment is only effective in a proportion of the patients, so considerable effort has been put into the development of new medications. The susceptibility to all major psychiatric disorders is, at least in part, genetic. Knowledge of the genes that underlie this susceptibility may lead to the identification of new drug targets and the development of more effective treatments. Therefore, numerous genetic studies in search for the genes involved in psychiatric disorders have been performed. Although results of both linkage and association studies have been inconsistent, several promising gene regions and candidate genes have been identified recently. In this article, we will review the strategies that proved to be successful in detecting genes for psychiatric disorders and we will provide some recommendations to increase the probability of detecting susceptibility genes in genetic studies of different designs.     

The development and maintenance of smooth muscle in control and aneurogenic amphibians (Ambystoma)

Summary Ultrastructural investigations showed that development and maintenance of smooth muscle was similar in control and aneurogenic amphibian larvae. This applies to both multi-unit and unitary smooth muscles. The gut musculature displayed a regional variation in smooth muscle morphology and a variety of intermuscular appositions even under conditions of nervelessness.Supported by NIH grant # AM 15732-04 and funds from the Muscular Dystrophy Association of America.The author thanks Ms. Shirley June for her excellent technical assistance and Mr. H. Popiela for preparation of some of the specimens.     

Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women

Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging.     

Calculation of the surface tension of planar interfaces by molecular simulations: from Lennard-Jones fluids to binary mixtures

The relative longevity of the research in the field of the molecular simulations of the liquid–vapour interfaces of Lennard-Jones (LJ) particles can be explained by the dependence of the surface tension on many methodological factors. After a few illustrations on the parameters that can impact the results of surface tension on the LJ interfaces, we establish the ability of the current methodologies to quantitatively predict the surface tension of various liquid–vapour interfaces of pure components at different temperatures. We also show that the methods perform very well for the reproduction of the interfacial tension of binary mixtures in a wide range of pressures.