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Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists.

The relationship between bovine tracheal muscle contraction and phosphoinositide metabolism was studied with the muscarinic agonists, methacholine, oxotremorine, and McN-A-343. Analysis of the dose-response curves for contraction and inositol phosphates accumulation with these agonists demonstrated a direct relationship between the two parameters, with a considerable reserve of inositol phosphate production for the full contractile agonists, methacholine and oxotremorine, and no reserve for the partial agonist, McN-A-343.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Prediction of calf volume during muscle contraction.

This study evaluated the relationship between calf volume changes and different intensities of maximum voluntary contractions (MVCs) of a lower limb performing plantar flexions. An electronic plethysmography instrument (EPI) was developed, and after testing for its reliability, it was used to measure calf volume changes. For EPI, the reliability correlation coefficients (r) to measure calf volume consistently were .98, .91, and .98 at 100% MVC, 80% MVC, and 60% MVC, respectively. There were also significant correlations between calf volume changes and the different intensities of MVC (MVC: r = .42, p < .011; 80% MVC: r = .41, p < .013; 60% MVC: r = .5, p < .002). The calf volume changes at different levels of muscle contractions also correlate significantly (upper calf: r = .55, p < .0002; middle calf: r = .58, p < .0007; and lower calf: r = .55, p < .002). The results indicated that EPI might be used as a reliable tool to predict the intensity of muscle contraction based on calf volume changes. Clinicians who use functional electrical stimulation to induce muscle contraction in people with muscle paralysis may use EPI to predict the volume changes during functional electrical stimulation-induced contractions and to deliver the proper amount of electrical stimulation, producing the desired level of contraction without undue stimulation or fatigue.

Adult↗

Hysteresis in corticospinal excitability during gradual muscle contraction and relaxation in humans.

Many studies have demonstrated that the firing behavior of single motor units varies in a nonlinear manner to the exerted torque during gradual muscle contraction and relaxation. However, it is unclear whether corticospinal excitability has such a hysteresis-like feature. In this study, we examined corticospinal excitability using transcranial magnetic stimulation (TMS) during gradual muscle contraction and relaxation for torque regulation in elbow flexor muscles. Eight healthy male subjects performed two different isometric elbow flexion tasks, namely, sinusoidal and tonic torque exertion tasks. In the sinusoidal task, the subjects sinusoidally increased and decreased the isometric elbow flexion torque (range of 0-15% of maximum voluntary contraction) at three different frequencies (0.33, 0.17, and 0.08 Hz). For each ascending (contraction: CON) and descending (relaxation: REL) period of the exerted torque, a single TMS was applied at 5 phases. In the tonic task, the elbow flexion torque was tonically exerted at 7 levels in a similar range as that in the sinusoidal task. EMG activities were recorded from the agonists, the biceps brachii (BB) and brachioradialis (BRD) muscles, and an antagonist, the triceps brachii (TB) muscle. The results demonstrated that the EMG activities of both the agonists and antagonist were larger in the CON period than the REL period, even when the exerted torque was the same. However, there were no significant differences in EMG activation profiles among the different frequencies of contraction. In BB and BRD, the motor-evoked potential (MEP) elicited by the TMS was also greater in the CON period than in the REL period. This CON-REL difference of MEP amplitudes was still observed when corrections were made for the increased EMG activities; that is, the MEP amplitudes to the identical EMG activities were greater in the CON period than in the REL period, and this phenomenon was more pronounced at higher frequencies. In addition, the degree to which sinusoidal MEPs exceeded tonic MEPs in the CON period and were smaller than tonic MEPs in the REL period became more pronounced at higher frequencies. On the other hand, there were significant correlations between the BB and BRD MEP amplitudes and the rate of change of elbow flexion/extension torque. These results indicate that corticospinal excitability during muscle contraction and relaxation has a neural hysteresis to the muscle activity, i.e., spinal motoneuronal activity, according to the rate of change of the exerted torque, i.e., muscle tension. This suggests that corticospinal excitability modulation depends not only on concurrent spinal motoneuronal activity and muscle tension but also on the time-series pattern of their changes during muscle contraction and relaxation.

Adult↗

Identification of the main generator source of longitudinal muscle contraction in the earthworm ventral nerve cord.

The main generator source of a longitudinal muscle contraction was identified as an M (mechanical-stimulus-sensitive) circuit composed of a presynaptic M-1 neuron and a postsynaptic M-2 neuron in the ventral nerve cord of the earthworm, Amynthas hawayanus, by simultaneous intracellular response recording and Lucifer Yellow-CH injection with two microelectrodes. Five-peaked responses were evoked in both neurons by a mechanical, but not by an electrical, stimulus to the mechanoreceptor in the shaft of a seta at the opposite side of an epidermis-muscle-nerve-cord preparation. This response was correlated to 84% of the amplitude, 73% of the rising rate and 81% of the duration of a longitudinal muscle contraction recorded by a mechanoelectrical transducer after eliminating the other possible generator sources by partitioning the epidermis-muscle piece of this preparation. The pre- and postsynaptic relationship between these two neurons was determined by alternately stimulating and recording with two microelectrodes. Images of the Lucifer Yellow-CH-filled M-1 and M-2 neurons showed that both of them are composed of bundles of longitudinal processes situated on the side of the nerve cord opposite to stimulation. The M-1 neuron has an afferent process (A1) in the first nerve at the stimulated side of this preparation and the M-2 neuron has two efferent processes (E1 and E3) in the first and third nerves at the recording side where their effector muscle cell was identified by a third microelectrode.

Animals↗

A new outlook on the energetics of muscle contraction.

Analysis of experimental data on two muscles demonstrates that, in contracting striated muscle, the total rate of ATP splitting, nu(t) (number of ATP molecules split per active myosin head per second), comprises of three separate components: nu(p), which is required for the generation of the contractile force P which is equal to the external load; nu(v) which is devoted to the development of the velocity of shortening V; and nu(w), which is responsible for the production of the mechanical power (PV). Nu(p) is proportional to P and nu(v) to V, which means that the sliding distance is independent of P. The mechanical power was found to be equal to the free energy change associated with the hydrolysis of nu(w), which means that the thermodynamic efficiency of the power-producing component is practically 100%. It is concluded that ATP hydrolysis is actually three different reactions. The analysis leads to Hill's force-velocity relationship. Its empirical constants a and b are expressed by thermodynamic and molecular parameters. The constant a was found to be inversely proportional to the sliding distance. The same considerations and conclusions should apply also to other muscles and to the movement under load of microtubules interacting with, e.g. kinesin.

Adenosine Triphosphate↗

Inertia and muscle contraction parameters for musculoskeletal modelling of the shoulder mechanism.

To develop a musculoskeletal model of the shoulder mechanism, both shoulders of seven cadavers were measured to obtain a complete set of parameters. Using antropometric measurements, the mass and rotational inertia of segments were estimated, followed by three-dimensional measurements of all morphological structures relevant for modelling, i.e. muscle origins and insertions, muscle bundle directions, ligament attachments and articular surfaces; all in relation to selected bony landmarks. Subsequently, muscle contraction parameters as muscle mass and physiological cross-sectional area were measured. The method of data collection and the results for inertia and muscle contraction parameters as prerequisities for modelling are described.

Aged↗

Changes in extracellular glutamate and pressor response during muscle contraction following AMPA-receptor blockade in the RVLM and CVLM.

We examined whether modulation of cardiovascular responses by administering 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, an AMPA-receptor antagonist) into the rostral (RVLM) or caudal (CVLM) ventrolateral medulla are mediated via changes in extracellular levels of glutamate. Microdialysis probes were inserted bilaterally into the RVLM or the CVLM. For the RVLM experiments (n=8), muscle contraction for 2 min increased mean arterial pressure (MAP) and heart rate (HR) by 18+/-3 mmHg and 24+/-5 bpm, respectively. Extracellular glutamate concentrations increased from 1.5+/-0.3 to 4.3+/-0.9 ng/5 microl during the contraction. Microdialysis of CNQX (1.0 microM) for 30 min into the RVLM attenuated the increases in MAP, HR, and glutamate concentration in response to a muscle contraction (8+/-2 mmHg, 11+/-3 bpm, and 2.2+/-0.7 ng/5 microl, respectively). Developed tensions did not change during contractions before and after CNQX. Microdialysis of CNQX into the CVLM (n=8) potentiated the contraction-evoked responses in MAP (19+/-3 vs. 34+/-3 mmHg) and HR (25+/-4 vs. 49+/-5 bpm) without a change in developed tension. Following CNQX perfusion into the CVLM, the levels of extracellular glutamate in the CVLM were also augmented during the contraction. Results suggests that AMPA-receptors within the RVLM and CVLM differentially modulate cardiovascular responses during static muscle contraction via increasing and decreasing, respectively, extracellular glutamate concentrations.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

A permanent prosthesis for converting in situ muscle contractions into hydraulic power for cardiac assist.

The key to utilizing muscle power for circulatory support lies with the development of a practical scheme by which contractile energy may be collected and efficiently delivered to the bloodstream. This work describes initial in vitro testing of a prototype muscle energy converter (MEC) designed to transform the power of in situ muscle contractions into hydraulic form. The MEC resembles a simple piston pump and is designed for implant beneath the humeral insertion of the latissimus dorsi muscle. Bench tests were conducted to measure component function and to characterize device performance under various hydraulic loads. Under simulated muscle-pull conditions, MEC energy transfer capacity was found to be 170 mJ/stroke while operating at peak efficiencies (i.e., > 98% of input power converted into hydraulic energy and preload work). Transfer efficiencies dropped from 96 to 38% as mean generated pressures increased from 23 to 36 N/cm2 due to metal bellows flexion. These results demonstrate that a significant amount of contractile energy can be efficiently transformed to hydraulic power via this mechanism.

Heart-Assist Devices↗

Modulation of pressor response to muscle contraction via monoamines following AMPA-receptor blockade in the ventrolateral medulla.

We hypothesized that cardiovascular responses to static muscle contraction are mediated via changes in extracellular concentrations of monoamines (norepinephrine, dopamine and serotonin) following the administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, an AMPA-receptor antagonist) into the rostral (RVLM) or caudal (CVLM) ventrolateral medulla. For the RVLM experiments (n= 8), a 2-min static muscle contraction increased the mean arterial pressure (MAP) and heart rate (HR) by 23 +/- 2 mmHg and 28 +/- 8 bpm, respectively. During this contraction, the concentrations of norepinephrine, dopamine, and serotonin within the RVLM increased by 278 +/- 52%, 213 +/- 23%, and 232 +/- 24%, respectively. Microdialysis of CNQX (1.0 microM) for 30 min into the RVLM attenuated the increases in MAP and HR ( 11 +/- 2 mmHg and 14 +/- 5 bpm) without a change in developed muscle tension. The levels of norepinephrine, dopamine, and serotonin within the RVLM were also attenuated. In contrast, microdialysis of CNQX into the CVLM (n= 8) potentiated the contraction-evoked responses in MAP ( 21 +/- 2 vs 33 +/- 5 mmHg) and HR ( 25 +/- 5 vs 46 +/- 8 bpm) without any effect on the monoamine levels within the CVLM region. These results suggest that AMPA-receptor blockade within the RVLM and CVLM has opposing effects on cardiovascular responses during static muscle contraction. In addition, such receptor blockade modulates extracellular concentrations of monoamines within the RVLM but not in the CVLM. These results provide evidence that AMPA receptors within the ventrolateral medulla play a role in exercise pressor reflex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Identification of dynamic myoelectric signal-to-force models during isometric lumbar muscle contractions.

A 14-muscle myoelectric signal (MES)-driven muscle force prediction model of the L3-L4 cross section is developed which includes a dynamic MES-force relationship and allows for cocontraction. Model parameters are estimated from MES and moments data recorded during rapid exertions in trunk flexion, extension, lateral bending and axial twist. Nine young healthy males participated in the experimental testing. The model used in the parameter estimation is of the output error type. Consistent and physically feasible parameter estimates were obtained by normalizing the RMS MES to maximum exertion levels and using nonlinear constrained optimization to minimize a cost function consisting of the trace of the output error covariance matrix. Model performance was evaluated by comparing measured and MES-predicted moments over a series of slow and rapid exertions. Moment prediction errors were on the order of 25, 30 and 40% during attempted trunk flexion-extensions, lateral bends and axial twists, respectively. The model and parameter estimation methods developed provide a means to estimate lumbar muscle and spine loads, as well as to empirically investigate the use and effects of cocontraction during physical task performances.

Adult↗

Muscle contraction increases the structural capacity of the lower leg: an in vivo study in the rat.

A model to study the contribution of muscle contraction to the structural capacity of the rat tibia was developed. The right lower leg was tested to failure in three-point ventral bending during electrically stimulated muscle contraction. The left lower leg was tested without stimulation, as a control. The mean ultimate bending moment for the stimulated legs was 0.603 Nm, compared with 0.492 Nm for the unstimulated legs (p < 0.001). The ultimate energy absorption was 0.313 and 0.188 J in the stimulated and unstimulated legs, respectively (p < 0.01). Fracture strength has been studied nearly exclusively in dissected bone stripped of all soft tissues. The present investigation suggests that studies of dissected bone are incomplete compared with the in vivo situation, as contraction of the muscles substantially increased the fracture strength of the lower leg in rats.

Animals↗

Cardiovascular responses and neurotransmission in the ventrolateral medulla during skeletal muscle contraction following transient middle cerebral artery occlusion and reperfusion.

We hypothesized that static skeletal muscle contraction-induced systemic cardiovascular responses, and central glutamate/GABA release in rostral (RVLM) and caudal ventrolateral medulla (CVLM), would be modulated by cerebral ischemia. In sham-operated rats, a 2-min tibial nerve stimulation induced static contraction of the triceps surae, evoked pressor responses, increased glutamate in both the RVLM and CVLM, decreased GABA in the CVLM, and increased GABA in the RVLM. In rats with a temporary 90-min left middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion, pressor responses during muscle contractions were attenuated, as were glutamate within the left RVLM and left CVLM. Glutamate within the right RVLM and right CVLM were unaltered and similar to those in sham rats. In contrast, GABA increases during muscle contractions were enhanced in the left RVLM and CVLM but changes within the right CVLM and RVLM were similar to those in sham rats. These results indicate that unilateral ischemia increases ipsilateral GABA/glutamate ratios during muscle contraction in the RVLM. In contrast, opposite changes in ipsilateral glutamate and GABA release within the RVLM and CVLM were observed following a 90-min right-sided MCAO followed by 24 h reperfusion. However, cardiovascular responses during muscle contraction were depressed following such an ischemic brain injury. These data suggest that transient ischemic brain injury attenuates cardiovascular responses to static exercise via modulating neurotransmission within the ventrolateral medulla.

Animals↗

Enhancement of neurokinin A-induced smooth muscle contraction in human urinary bladder by mucosal removal and phosphoramidon: relationship to peptidase inhibition.

Neurokinin A (NKA) is potent in contracting the human detrusor muscle. Here, we have investigated whether these contractile responses are influenced by the presence of the mucosa, by the peptidase inhibitor phosphoramidon or by possible modulators, prostaglandins and nitric oxide. Contractile responses to neurokinin A were unaffected by indomethacin or N-omega-nitro-L-arginine, but were significantly reduced in strips containing mucosa. Phosphoramidon, an inhibitor of neutral endopeptidase 24.11 (neprilysin, CD10), was ineffective at 10 microM, but at 100 microM, significant increase in the maximum response was achieved by neurokinin A in detrusor strips with and without mucosa. In immunohistochemical studies, neutral endopeptidase immunoreactivity occurred in peripheral nerve trunks in the detrusor and in a fibrous meshwork in the subepithelial lamina propria. Our data indicate that neutral endopeptidase is present in bladder mucosa and detrusor, and support the concept that this metalloprotease and/or related enzymes are important in regulating the actions of tachykinins.

Aged↗

Darmstoff analogues. 2. Ring and side-chain effects on smooth-muscle contraction.

2-cis-delta 8-Heptadecenyl-4-(hydroxymethyl)-1,3-dioxolane monosodium phosphate (1b) has been shown to be present as a major component of Darmstoff in mammalian intestine and to be a potent inducer for contraction of intestinal smooth muscle. The analogous 2-pentadecyl material 1a, also found abundantly in the intestine, is inactive. In this study, synthesis of phosphorylated hydroxymethyl-1,4-dioxanes, -tetrahydrofurans, -cyclopentanes, and -oxathiolanes bearing both oleyl and palmityl side chains is reported. Of these, 2-(hydroxymethyl)-5-cis-delta 8-heptadecenyl-1,4-dioxane monosodium phosphate (2b) exhibits about 12% of the activity of 1b. Its pentadecyl analogue 2a, like 1a, is totally inactive, as are all other compounds prepared. The results indicate that Darmstoff-like compounds exhibit specific chemical requirements for activity and that where activity is encountered, the side-chain specificity noted in 1a and 1b can be preserved.

Animals↗