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Differential activation of octopaminergic (DUM) neurones via proprioceptors responding to flight muscle contractions in the locust

The synaptic potentials generated in neuromodulatory octopaminergic dorsal unpaired median (DUM) neurones by afferents excited by twitch contractions of a dorso-ventral flight muscle were investigated in the locust. Responses to stimulation of the metathoracic wing elevator muscle 113 were obtained in locusts in which all sensory feedback from the thorax had been removed, except for feedback from the thoracic chordotonal organs, the axons of which enter via the purely sensory nerve 2. Afferents in nerve 2C, which originates from two chordotonal organs, responded reliably to twitch contractions of this flight muscle. Octopaminergic neurones innervating leg muscles (DUM5 neurones) received depolarising inputs and often spiked following stimulation of the muscle. In contrast, those innervating the wing muscles themselves (DUM3 and DUM3,4 neurones) received inhibitory inputs. The responses of DUM3,4,5 neurones, which project mainly to leg muscles, were more complex: most were excited by twitch contractions of M113 but some were inhibited. DUMDL, which innervates the dorsal longitudinal indirect flight muscles, showed no clear response. Direct stimulation of nerve 2C evoked depolarising inputs and spikes in DUM5 neurones and hyperpolarising inputs in DUM3 and DUM3,4 neurones. Our data suggest that sensory feedback from thoracic chordotonal organs, which are known to be activated rhythmically during flight, contributes to the differential activation of efferent DUM neurones observed during flight.

Journal Article↗

Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction.

BACKGROUND: Cyclosporine immunosuppression for organ transplantation is associated with hypertension and nephrotoxicity. Because the effects of cyclosporine as an immunosuppressant are mediated by the effect of cyclosporine as a phosphatase inhibitor, and phosphatase inhibitors are potent vascular smooth muscle contractile agents, we hypothesized that cyclosporine might induce contraction of the renal artery vascular smooth muscle directly. METHODS: Strips of bovine renal, carotid, superior mesenteric, or coronary arteries were obtained fresh from an abattoir. The strips were equilibrated in a muscle bath, and the contractile responses to cyclosporine and FK506 were determined. RESULTS: Cyclosporine (50 to 5000 micrograms/ml), but not FK506, induced rapidly developing, sustained contractions of renal and coronary artery smooth muscle. The magnitude of the cyclosporine-induced contractions of carotid and superior mesenteric artery smooth muscles was significantly less. The magnitude of renal artery smooth muscle contractions induced by cyclosporine was enhanced in the presence of an intact endothelium. CONCLUSIONS: Although these effects occurred in vitro to relatively high doses of cyclosporine, these data suggest that cyclosporine may selectively induce renal artery smooth muscle contraction through activation of the Ca(2+)-dependent phosphatase (calcineurin) in the smooth muscle, and these contractions may be enhanced by the release of endothelial-derived contracting factors.

Animals↗

Species-dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice.

The peptide ligand neuromedin U (NMU) has been implicated in an array of biological activities, including contraction of uterine, intestinal and urinary bladder smooth muscle. However, many of these responses appear to be species-specific. This study was undertaken to fully elucidate the range of smooth muscle-stimulating effects of NMU in rats, mice and guinea-pigs, and to examine the extent of the species differences. In addition, the NMU1 receptor knockout mouse was used to determine which receptor subtype mediates the contractile responses generated by NMU in the mouse. A range of isolated organ in vitro bioassays were carried out, which were chosen to re-confirm previous literature reports (uterine and stomach fundus contraction) and also to explore potentially novel smooth muscle responses to NMU. This investigation uncovered a number of previously unidentified NMU-mediated responses: contraction of rat lower esophageal sphinster (LES), rat ileum, mouse gallbladder, enhancement of electrically evoked contractions in rat and mouse vas deferens, and a considerable degree of cross-species differences. Studies using the NMU1 receptor knockout mice revealed that in the mouse fundus and gallbladder assays the NMU contractile response was mediated entirely through the NMU1 receptor subtype, whereas, in assays of mouse uterus and vas deferens, the response to NMU was unchanged in the NMU1 receptor knockout mouse, suggesting that the NMU response may be mediated through the NMU2 receptor subtype. NMU receptor subtype-selective antagonists are required to further elucidate the role of the individual receptor subtypes.

Animals↗

Acute hypoxemia does not increase the oxidative stress in resting and contracting muscle in humans.

In healthy humans sustaining static handgrip at 60% of maximal voluntary contraction (MVC) until exhaustion, we measured the venous blood concentration of reduced ascorbic acid (RAA) and thiobarbituric acid reactive substances (TBARS), respectively, used as markers of the post-exercise oxidative stress and lipid peroxidation. Measurements were conducted in normoxemia, then during a 30-min period of hypoxemia (PaO2 = 56 mmHg) produced by inhalation of an hypoxic gas mixture. Compared to normoxemia, hypoxemia did not significantly modify the resting concentrations of TBARS and RAA, and did not affect the consumption of ascorbic acid after 60% MVC but suppressed the post-exercise TBARS increase. We conclude that acute hypoxemia does not modify the production of oxygen free radicals after strenuous static efforts and even seems to attenuate the lipid peroxidation.

Adult↗

The use of real-time ultrasound imaging for biofeedback of lumbar multifidus muscle contraction in healthy subjects.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To determine if the provision of visual biofeedback using real-time ultrasound imaging enhances the ability to activate the multifidus muscle. BACKGROUND: Increasingly clinicians are using real-time ultrasound as a form of biofeedback when re-educating muscle activation. The effectiveness of this form of biofeedback for the multifidus muscle has not been reported. METHODS AND MEASURES: Healthy subjects were randomly divided into groups that received different forms of biofeedback. All subjects received clinical instruction on how to activate the multifidus muscle isometrically prior to testing and verbal feedback regarding the amount of multifidus contraction, which occurred during 10 repetitions (acquisition phase). In addition, 1 group received visual biofeedback (watched the multifidus muscle contract) using real-time ultrasound imaging. All subjects were reassessed a week later (retention phase). RESULTS: Subjects from both groups improved their voluntary contraction of the multifidus muscle in the acquisition phase (P<.001) and the ability to recruit the multifidus muscle differed between groups (P<.05), with subjects in the group that received visual ultrasound biofeedback achieving greater improvements. In addition, the group that received visual ultrasound biofeedback retained their improvement in performance from week 1 to week 2 (P>.90), whereas the performance of the other group decreased (P<.05). CONCLUSION: Real-time ultrasound imaging can be used to provide visual biofeedback and improve performance and retention in the ability to activate the multifidus muscle in healthy subjects.

Adult↗

H reflex excitability following voluntary muscle contraction of different duration.

The importance of the duration of contraction on the excitability of the motoneuronal pool was evaluated by measuring the H reflex from soleus muscle after short and long contractions at constant effort equal to 60% maximal voluntary contraction (MVC); the difference between the amplitude of H reflex at rest and after contraction of different duration was evaluated in 10 normal subjects and in one hemiparetic patient. The authors found a significant inhibition of H reflex after contraction of 10 seconds and after 40 seconds and a longer duration of the inhibition after 40 seconds. In the hemiparetic patient the H reflex did not show inhibition which suggests a possible reduction of the presynaptic inhibition, and a lack of modulation of the motoneuronal pool after contraction.

Adult↗

Regulation of glycerinated smooth muscle contraction and relaxation by myosin phosphorylation.

Regulation of isometric force maintenance, isotonic shortening velocity, and muscle stiffness by myosin phosphorylation was examined during both contraction and relaxation of chemically permeabilized (glycerinated) rat uterine smooth muscle. Phosphorylation of the 20,000-Da light chain of myosin (LC20) was manipulated by varying the calcium activity of the bathing solution or by thiophosphorylation of LC20 in the presence of ATP gamma S. With saturating calcium and calmodulin, LC20 phosphorylation was 0.43 mol PO4/mol LC20. This increased to 0.92-0.96 mol PO4/mol LC20 on addition of ATP gamma S. Over the entire range of phosphorylation, there was a significant (P less than 0.001) linear correlation between force and phosphorylation. Stiffness increased monotonically with increasing force; however, the relationship was nonlinear, with stiffness increasing faster at lower levels of activation. Force, stiffness, shortening velocity, and LC20 phosphorylation were compared at identical calcium activities during steady-state conditions of partial contraction and partial relaxation. The ratio of the value of each parameter measured during relaxation to that measured during contraction was 1.11 for force, 1.09 for stiffness, 1.01 for shortening velocity, and 0.83 for LC20 phosphorylation. These results support the hypothesis that contraction and relaxation in glycerinated rat uterine muscle are regulated primarily by phosphorylation and dephosphorylation of LC20.

Adenosine Triphosphate↗

Presynaptic inhibition evoked by muscle contraction.

1. Contractions of flexor and extensor muscles of the knee and ankle were used to investigate presynaptic inhibition at the spinal level.2. Contractions evoked dorsal root potentials, and increased the excitability of the central terminals of group Ia, Ib and low threshold cutaneous primary afferent fibres.3. The monosynaptic reflexes recorded in response to stimulation of flexor or extensor muscle nerves were depressed, in the presence of strychnine hydrochloride 0.1 mg/kg I.V., by the contractions.4. It is suggested that these presynaptic inhibitory effects are largely due to the activation of Golgi tendon organs by contraction.

Journal Article↗

Effect of almitrine on upper airway muscle contraction in young and old rats.

The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in young and old rats. In young rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships or frequency-tension relationship in both muscles. Almitrine significantly increased resistance to fatigue in both muscles. In old rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships, frequency-tension relationship or fatigue in both muscles. These results show that almitrine, in both young and old rats, has no effect on most of the contractile properties of isolated geniohyoid and sternohyoid muscles. However, almitrine increases resistance to fatigue in both muscles in young but not in old rats.

Age Factors↗

Motor unit activities during maintained voluntary muscle contraction at constant levels in man.

Activities of motor units of human tibialis anterior muscle were studied when the subject maintained the force of the muscle at a constant level voluntarily. Motor units were classified into two main groups according to their discharge frequencies and their tensions. Those units which were recruited from the beginning of the contraction and discharged tonically throughout yielded low tensions and units which showed discharge only for a limited period produced higher tensions.

Adult↗

Gender modulates the energy cost of muscle contraction in untrained healthy subjects. A 31P magnetic resonance spectroscopy analysis.

The forearm flexor muscles of 56 untrained volunteers (26 women and 30 men) were examined by 31P magnetic resonance spectroscopy, during a rest-exercise-recovery protocol, in order to document the impact of gender on muscle energetics. Absolute concentrations of high-energy phosphate compounds, intracellular pH and rates of aerobic and anaerobic ATP production were calculated. An inverse correlation was found between body mass index (BMI) and power output in women but not in men. After correcting for power output and BMI, the measured energy cost of contraction was twice larger for women than for men. This increase was also reflected in larger ATP production from aerobic and anaerobic pathways. This higher energy cost might be explained in part by differences in local muscle mass, a higher impact of fatness, but also by a reduced metabolic efficiency of muscle fibers in untrained women.

Adenosine Triphosphate↗

Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus.

Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 micros, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones.

Acetylcholine↗