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At least 199 records · Page 11Linked to original sources

Effect of phospholipase C inhibitor U-73122 on antigen-induced airway smooth muscle contraction in guinea pigs.

The importance of phospholipase C (PLC) in airway smooth muscle contraction was studied, using an inhibitor of PLC, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl] amino]hexyl]-1H-pyrrole-2,5-dione (U-73122). Tracheas from ovalbumin (OA)-sensitized guinea pigs contracted rapidly after exposure to low concentrations of antigen (OA). However, tracheas treated with U-73122 for 10 min prior to the addition of antigen, demonstrated a 3 log rightward shift in the OA dose-response curve with an IC50 of 7 microM. The analogue of U-73122, 1-[6[[17 beta-3-methoxyestra-1,3,5 trien-17-yl]amino]hexyl]-2,5-pyrrolidine-dione (U-73433), was approximately 5-fold less active in inhibiting smooth muscle contraction. In addition to the inhibition of antigen-induced smooth muscle contraction, U-73122 inhibited carbachol- and leukotriene D4-induced smooth muscle contraction. Furthermore, U-73122 inhibited in a dose-dependent manner antigen-induced histamine release from guinea pig tracheal tissue. The inhibition of smooth muscle contraction by U-73122 correlated well with the inhibition of polyphosphoinositide mediates smooth muscle contractile responses to muscarinic agonists and leukotrienes as well as antigenic-induced contraction.

Animals↗

Hyperpyrexia associated with sustained muscle contractions: an alternative diagnosis to central fever.

Muscle activity is the principal source of body heat production, and elevated core body temperatures may occur in healthy exercising persons. Hyperpyrexia from sustained tonic muscle contractions can also occur in a number of pathological conditions. The present case of hyperpyrexia associated with dystonic posturing and sustained muscle contraction in a child with encephalopathy illustrates the importance of recognizing muscular activity in the generation of fever of unknown origin following central nervous system injury. The pathophysiology, clinical features, and management of this uncommon cause of fever are discussed.

Brain Diseases↗

Bioassays of smooth muscle contracting agents in cotton mill dust and bract extracts: arachidonic acid metabolites as possible mediators of the acute byssinotic reaction.

Byssinosis is an occupational respiratory disease contracted by cotton mill workers who inhale cotton mill dust. The acute byssinotic reaction is characterized by a drop in the 1-sec forced expiratory volume (FEV1.0) on Monday following a weekend's absence from work. This physiological reaction is the result of the contraction of bronchial smooth muscle, which causes narrowing of small airways. An isolated tissue bath technique was used to assay smooth muscle contractions induced by cotton dust extract (CDE) and cotton bract extract (CBE). CBE-induced contractions of rat stomach smooth muscle were blocked (82%) by 100 ng/ml methysergide (blocks 5-hydroxytryptamine (5HT) 100%); CDE was not significantly blocked by methysergide (13%). CDE-induced contractions were blocked (100%) by 25 micrograms/ml indomethacin and 100 micrograms/ml salicylic acid (blocks prostaglandin F2 alpha (PGF2 alpha) 100%). The portion of CBE contracting ability not blocked by methysergide was blocked totally by indomethacin. Blocking agents ineffective against CDE or CBE include atropine (acetylcholine blocker), pyrilamine maleate and diphenhydramine (histamine blockers), imidazole and 7-(1-imidazolyl)heptanoic acid (7IHA) (thromboxane blockers), and carboxypeptidase B2 (kinin blocker). The data suggest that cotton bract contains 5HT, which is responsible for a majority of the CBE-induced contraction and a minority of the CDE-induced contraction. The data also suggest that cotton dust and bract contain a substance which causes the release of PGF2 alpha which in turn causes the contraction of smooth muscle. This substance is responsible for a majority of the CDE-induced and a minority of the CBE-induced contractions. Radioimmunoassay (RIA) confirmed PGF2 alpha release from rat fundal smooth muscle when exposed to CDE and CBE. Increased synthesis and release of arachidonic acid metabolites might be a major mechanism in the bronchoconstriction observed in the acute byssinotic reaction.

Acute Disease↗

Myotonic myopathy with painful muscle contractions and decrease of symptoms by cold.

Myotonic reaction and paresis accompanied by painful muscle contractions limited to the upper limbs, which decrease remarkably in the cold, were observed in a 29 year old man. The histological investigation revealed minimal non-specific signs of myopathy. The biochemical studies of muscular tissue contained a normal amount of myophosphorylase, acid maltase and glycogen. Ischemic work induced normal elevation of venous lactate. The activities of CPK, LDH and SGOT in the blood serum were occasionally increased. The EMG showed typical myotonic bursts and electrical silence during painful muscle contractions. Repetitive high frequency stimulation demonstrated a clear initial increase of the amplitude of action potentials followed by a decrease in the contracted muscle. The father of the patient suffered from dystrophia myotonica. This coincidnece suggests that this myotonic myopathy is a variant of dystrophia myotonica.

Cold Temperature↗

Exercise-induced skeletal muscle damage and adaptation following repeated bouts of eccentric muscle contractions.

Repeated bouts of eccentric muscle contractions were used to examine indirect indices of exercise-induced muscle damage and adaptation in human skeletal muscle. Twenty-four subjects (18 females, 6 males) aged 20.0 +/- 1.4 years (mean +/- S.D.) performed an initial bout of either 10 (n = 7), 30 (n = 9) or 50 (n = 8) maximum voluntary eccentric contractions of the knee extensors, followed by a second bout of 50 contractions 3 weeks later using the same leg. Muscle soreness was elevated after all bouts (P < 0.05, Wilcoxon test), although the initial bout reduced the soreness associated with the second bout. Force loss and a decline in the 20:100 Hz percutaneous electrical myostimulation force ratio were observed after all exercise bouts (P < 0.01). Serum creatine kinase activity was elevated following the initial bouts of 30 and 50 repetitions (P < 0.01), but there was no increase following 10 repetitions. No increase in serum creatine kinase activity was observed in any group following the second bout of contractions (P > 0.05). We conclude that skeletal muscle adaptation can be brought about by a single bout of relatively few eccentric muscle contractions. Increasing the number of eccentric muscle repetitions did not result in an increased prophylactic effect on skeletal muscle.

Adaptation, Physiological↗

[The GABA-ergic regulation of the Lymnaea stagnalis (L.) dorsal longitudinal muscle contractions].

Presence of GABA-immunoreactive fibres in the nerve cervicalis inferior was shown as well as their regulatory effects upon contractions of the dorsal longitudinal muscle in Lymnaea stagnalis. The exogenous GABA affected the amplitude of evoked muscle contractions diminishing them at concentrations from 10(-8) M and augmenting them from above 10(-5) M. Picrotoxin produced opposite effects on the muscle contractions in the same concentration range. Bicucullin did not affect the contractions. The findings are discussed from the standpoint of the supposed functional heterogeneity of the GABA receptors in the mollusc nerve-muscle junction.

Animals↗

The effect of general anesthetic agents, ouabain, and aldosterone on striated muscle contraction in toad.

Na+ and K+ transport, resting potentials, action potentials, and muscle contraction are interrelated in the excitation-contraction coupling process. Since anesthetics affect the electrogenic Na+ transport mechanism in the toad bladder model and the coupled Na+, K+ transport in muscle, the authors tested the hypothesis that the effects of inhalation anesthetics on ion transport and muscle contraction are parallel. In this study, the effects were assessed of 4 inhalation anesthetics and, for comparison, the effects of ouabain and aldosterone, on contractions of toad sartorius muscle. Cyclopropane, N2O, ether, and halothane, as well as ouabain and aldosterone, increased twitch height in low concentrations. Halothane, ether, and ouabain decreased twitch height in high concentrations. The effect of cyclopropane and N2O, oubain, and aldosterone on muscle contraction closely paralleled their action on electrogenic Na+ transport. This observation supports the hypothesis that the influence of these agents on muscle contraction is linked to the effect on active ion transport or that both effects are equally sensitive to anesthetic agents.

Aldosterone↗

Mechanisms of direct inhibitory action of propofol on uterine smooth muscle contraction in pregnant rats.

BACKGROUND: Although propofol directly inhibits uterine smooth muscle contraction, the mechanisms of this effect are still unknown. The current study aimed to clarify the mechanisms of the inhibitory effect of propofol on oxytocin-induced uterine smooth muscle contraction by measuring (1) the concentration of intracellular free Ca(2+) ([Ca(2+)](i)) simultaneously with muscle tension, (2) the amount of intracellular inositol 1,4,5-triphosphate ([IP(3)](i)), and (3) voltage-dependent Ca(2+) channel (VDCC) activity. METHODS: Uterine smooth muscle tissues were obtained from pregnant rats (in late gestation). [Ca(2+)](i) with isometric tension was monitored by the 500-nm light emission ratio of preloaded Ca(2+) indicator fura-2. [IP(3)](i) and VDCC activity were measured by radioimmunoassay and patch clamp techniques, respectively. The uterine smooth muscle was stimulated by 20 nm oxytocin and exposed to propofol (10(-7) approximately 10(-4) m). RESULTS: Propofol had significant inhibitory effects on oxytocin-induced uterine smooth muscle contraction and increased [Ca(2+)](i) in pregnant rats in a dose-dependent manner, without affecting the agonist-receptor binding affinity. Propofol inhibited the increase in [IP(3)](i) induced by oxytocin. Propofol also inhibited VDCC activity in both activated and inactivated states. The solvent Intralipid had no effects on these parameters. CONCLUSIONS: Propofol inhibits oxytocin-induced uterine smooth muscle contraction, at least in part, by decreasing [Ca(2+)](i) without affecting agonist-receptor binding; the inhibitory effect of propofol on [Ca(2+)](i) might be mediated both by a decrease in [IP(3)](i) and by inhibition of VDCC activity.

Anesthetics, Intravenous↗

Regulation of human muscle contraction at the cellular and molecular levels.

The rat is the most extensively characterized species with regard to regulation of muscle contraction and myofibrillar protein isoform expression, but there is reason to question whether results from small mammals, such as the rat, can be extrapolated directly to larger mammals, such as man. Studies of human muscle contraction have primarily used different in vivo muscle function measurements, i.e. measurements of force at different speeds of movement during electrical stimulation or voluntary activation. These measurements give important information on overall muscle function, but they are of limited value for our understanding of regulation of muscle contraction. In basic science, cellular- and molecular-physiological methods have been used for many years, but these techniques have so far only rarely been used in studies of human muscle contraction. Detailed studies of human muscle contraction can be performed in the short muscle fibre segments obtained by the percutaneous muscle biopsy technique both at the cellular and molecular level. The skinned fibre preparation in combination with a novel in vitro motility assay offers a unique possibility to investigate regulation of human muscle contraction at the cellular and molecular levels in the same muscle cell segment in both health and disease, i.e. in muscle cells characterized according to the type and amount of expressed myofibrillar protein isoforms.

Actin Cytoskeleton↗

Relationship between urethral and vaginal pressures during pelvic muscle contraction. The Continence Program for Women Research Group.

Condensation is the performance of an effective pelvic muscle contraction increases urethral and vaginal pressures and is independent of demographic, clinical, and urodynamic factors. Our objective was to examine the relationship between urethral closure pressure and vaginal pressure during a pelvic muscle contraction in minimally trained women. Our secondary aim was to determine whether demographic, clinical, or urodynamic factors predict pelvic muscle contraction performance. Two hundred two women with urinary incontinence underwent multichannel urodynamic evaluation, including urethral profilometry and measurement of vaginal pressure during pelvic muscle contraction. One hundred forty-four women were diagnosed with genuine stress incontinence, 28 with detrusor instability, and 30 with mixed incontinence. Urethral and vaginal pressures correlated significantly during pelvic muscle contraction (P < or = 0.006). The ability to perform an adequate pelvic muscle contraction was independent of subject age, parity, hormonal or hysterectomy status, clinical severity, urethral support, and urethral profilometry measures (P > or = 0.42).

Aged↗

Synchrony between circular and longitudinal muscle contractions during peristalsis in normal subjects.

The current understanding is that longitudinal muscle contraction begins before and outlasts circular muscle contraction during esophageal peristalsis in normal subjects. The goal of our study was to reassess the relationship between the contractility of two muscle layers using novel ways to look at the muscle contraction. We studied normal subjects using synchronized high-frequency ultrasound imaging and manometry. Swallow-induced peristalsis was recorded at 5 and 10 cm above the lower esophageal sphincter (LES). Ultrasound (US) images were analyzed for muscle cross-sectional area (CSA) and circularity index of the esophagus during various phases of esophageal contraction. A plot of the M mode US image, muscle CSA, and esophageal circularity index was developed to assess the temporal correlation between various parameters. The muscle CSA wave began before and lasted longer than the contraction pressure wave at both 5 and 10 cm above the LES. M mode US images revealed that the onset of muscle CSA wave was temporally aligned with the onset of lumen collapse. The peak muscle CSA occurred in close proximity with the peak pressure wave. The esophagus started to become more circular (decrease in circularity index) with the onset of the muscle CSA wave. The circularity index and muscle CSA returned to the baseline at approximately the same time. In conclusion, the onset of lumen collapse and return of circularity index of the esophagus are likely to be the true markers of the onset and end of circular muscle contraction. Circular and longitudinal muscle layers of the esophagus contract in a precise synchronous fashion during peristalsis in normal subjects.

Adult↗

The neuromuscular transform: the dynamic, nonlinear link between motor neuron firing patterns and muscle contraction in rhythmic behaviors.

The nervous system issues motor commands to muscles to generate behavior. All such commands must, however, pass through a filter that we call here the neuromuscular transform (NMT). The NMT transforms patterns of motor neuron firing to muscle contractions. This work is motivated by the fact that the NMT is far from being a straightforward, transparent link between motor neuron and muscle. The NMT is a dynamic, nonlinear, and modifiable filter. Consequently motor neuron firing translates to muscle contraction in a complex way. This complexity must be taken into account by the nervous system when issuing its motor commands, as well as by us when assessing their significance. This is the first of three papers in which we consider the properties and the functional role of the NMT. Physiologically, the motor neuron-muscle link comprises multiple steps of presynaptic and postsynaptic Ca(2+) elevation, transmitter release, and activation of the contractile machinery. The NMT formalizes all these into an overall input-output relation between patterns of motor neuron firing and shapes of muscle contractions. We develop here an analytic framework, essentially an elementary dynamical systems approach, with which we can study the global properties of the transformation. We analyze the principles that determine how different firing patterns are transformed to contractions, and different parameters of the former to parameters of the latter. The key properties of the NMT are its nonlinearity and its time dependence, relative to the time scale of the firing pattern. We then discuss issues of neuromuscular prediction, control, and coding. Does the firing pattern contain a code by means of which particular parameters of motor neuron firing control particular parameters of muscle contraction? What information must the motor neuron, and the nervous system generally, have about the periphery to be able to control it effectively? We focus here particularly on cyclical, rhythmic contractions which reveal the principles particularly clearly. Where possible, we illustrate the principles in an experimentally advantageous model system, the accessory radula closer (ARC)-opener neuromuscular system of Aplysia. In the following papers, we use the framework developed here to examine how the properties of the NMT govern functional performance in different rhythmic behaviors that the nervous system may command.

Animals↗

Human brain activation during sustained and intermittent submaximal fatigue muscle contractions: an FMRI study.

During prolonged submaximal muscle contractions, electromyographic (EMG) signals typically increase as a result of increasing motor unit activities to compensate for fatigue-induced force loss in the muscle. It is thought that cortical signals driving the muscle to higher activation levels also increases, but this has never been experimentally demonstrated. The purpose of this study was to quantify brain activation during submaximal fatigue muscle contractions using functional magnetic resonance imaging (fMRI). Twelve volunteers performed a sustained handgrip contraction for 225 s and 320 intermittent handgrip contractions ( approximately 960 s) at 30% maximal level while their brain was imaged. For the sustained contraction, EMG signals of the finger flexor muscles increased linearly while the target force was maintained. The fMRI-measured cortical activities in the contralateral sensorimotor cortex increased sharply during the first 150 s, then plateaued during the last 75 s. For the intermittent contractions, the EMG signals increased during the first 660 s and then began to decline, while the handgrip force also showed a sign of decrease despite maximal effort to maintain the force. The fMRI signal of the contralateral sensorimotor area showed a linear rise for most part of the task and plateaued at the end. For both the tasks, the fMRI signals in the ipsilateral sensorimotor cortex, prefrontal cortex, cingulate gyrus, supplementary motor area, and cerebellum exhibited steady increases. These results showed that the brain increased its output to reinforce the muscle for the continuation of the performance and possibly to process additional sensory information.

Adult↗

Somatosensory-evoked potentials are influenced differently by isometric muscle contraction of stimulated and non-stimulated hand in humans.

Chronic pain is associated with motor dysfunctions, and stimulation of the motor cortex has been shown to alleviate chronic pain. Recently Nakata et al. [Pain 107 (2004) 91-98] showed differentiated patterns of neuromagnetic evoked fields following painful laser stimulation during phasic movements of stimulated and non-stimulated hand. Phasic movements and static contractions differ in their functional activation of the motor cortices. Therefore, we decided to analyze the effects of isometric contractions of intrinsic right and left hand muscles on cortical sources of somatic-evoked potentials related to a painful galvanic stimulation of the right middle finger. Using spatio-temporal source dipole analysis of 111 electroencephalographic signals in 10 right-handed men, source activities were evaluated in the left primary somatosensory cortex (S1), left (S2(L)) and right (S2(R)) secondary somatosensory cortex, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC). Ipsilateral hand muscle contraction was associated with a decrease of source activity in S1 and with subsequent increases in S2(L) and the PCC. Contralateral hand muscle contraction was accompanied by a decrease of source activity in bilateral S2 cortices followed by decreases in the S1 and anterior cingulate cortex. Results suggest early suppression of source activity in S1 during ipsilateral hand muscle contractions and in bilateral S2 during contralateral hand muscle contractions.

Adult↗

Influence of sodium pumping on smooth muscle contraction.

Isolated capsular muscle from cat spleen did not contract on exposure to a potassium-free bathing fluid. After exposure to conditions favouring downhill sodium and potassium movement (i.e. stimulation by noradrenaline in the absence of external potassium), subsequent reactivation of the sodium pump inhibited responses to noradrenaline. Under these special conditions, but not normally, the sodium pump may be behaving in an electrogenic manner.

Animals↗

Rapid vasodilation in response to a brief tetanic muscle contraction.

To test the hypothesis that vasodilation occurs because of the release of a vasoactive substance after a brief muscle contraction and to determine whether acetylcholine spillover from the motor nerve is involved in contraction-induced hyperemia, tetanic muscle contractions were produced by sciatic nerve stimulation in anesthetized dogs (n = 16), instrumented with flow probes on both external iliac arteries. A 1-s stimulation of the sciatic nerve at 1. 5, 3, and 10 times motor threshold increased blood flow above baseline (P < 0.01) for 20, 25, and 30 s, respectively. Blood flow was significantly greater 1 s after the contraction ended for 3 and 10 x motor threshold (P < 0.01) and did not peak until 6-7 s after the contraction. The elevations in blood flow to a 1-s stimulation of the sciatic nerve and a 30-s train of stimulations were abolished by neuromuscular blockade (vecuronium). The delayed peak blood flow response and the prolonged hyperemia suggest that a vasoactive substance is rapidly released from the contracting skeletal muscle and can affect blood flow with removal of the mechanical constraint imposed by the contraction. In addition, acetylcholine spillover from the motor nerve is not responsible for the increase in blood flow in response to muscle contraction.

Acetylcholine↗

Ca2+-independent smooth muscle contraction. a novel function for integrin-linked kinase.

Smooth muscle contraction follows an increase in cytosolic Ca(2+) concentration, activation of myosin light chain kinase, and phosphorylation of the 20-kDa light chain of myosin at Ser(19). Several agonists acting via G protein-coupled receptors elicit a contraction without a change in [Ca(2+)](i) via inhibition of myosin light chain phosphatase and increased myosin phosphorylation. We showed that microcystin (phosphatase inhibitor)-induced contraction of skinned smooth muscle occurred in the absence of Ca(2+) and correlated with phosphorylation of myosin light chain at Ser(19) and Thr(18) by a kinase distinct from myosin light chain kinase. In this study, we identify this kinase as integrin-linked kinase. Chicken gizzard integrin-linked kinase cDNA was cloned, sequenced, expressed in E. coli, and shown to phosphorylate myosin light chain in the absence of Ca(2+) at Ser(19) and Thr(18). Subcellular fractionation revealed two distinct populations of integrin-linked kinase, including a Triton X-100-insoluble component that phosphorylates myosin in a Ca(2+)-independent manner. These results suggest a novel function for integrin-linked kinase in the regulation of smooth muscle contraction via Ca(2+)-independent phosphorylation of myosin, raise the possibility that integrin-linked kinase may also play a role in regulation of nonmuscle motility, and confirm that integrin-linked kinase is indeed a functional protein-serine/threonine kinase.

Amino Acid Sequence↗