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PubMed2004

Direct inhibition of rat detrusor muscle contraction by erythromycin.

PURPOSE: Detrusor instability is a common problem in the elderly, which is usually treated with anti-cholinergic medication. This study investigates the effect of erythromycin on rat detrusor muscle contractile response to characterise its potential as an alternative inhibitor of bladder muscle contraction. MATERIALS AND METHODS: Strips of rat detrusor muscle were suspended in a perfusion organ bath. The contractile response to direct muscle stimulation, electrical field stimulation (EFS, 0.5-60 Hz), carbachol (10(-5) M), and potassium (10-80 x 10(-3) M) were determined before and after the addition of erythromycin (10(-4)-10(-3) M). The contractile response to carbachol (10(-5) M) in the presence of nifedipine (10(-8) or 10(-6) M) or in calcium-free Kreb's solution was also determined in the absence and presence of erythromycin. RESULTS: Erythromycin 5 x 10(-4) M inhibited the maximum contractile response to EFS, carbachol, and potassium by 38% (P < 0.01), 62% (P < 0.001), and 17% (P < 0.05), respectively, but did not significantly reduce the response to direct muscle stimulation. The atropine-resistant component of EFS-evoked contraction was inhibited by 19.5% (P < 0.01) in the presence of erythromycin. In calcium-free Krebs solution, the maximum contractile response to carbachol was reduced by 42% of control (P < 0.0001) and nifedipine 10(-8) M had no additional effect. When erythromycin 5 x 10(-4) M was added together with nifedipine 10(-8) M, the response to carbachol was inhibited by a further 25% (P < 0.005). CONCLUSIONS: Erythromycin inhibits rat detrusor muscle contraction through the inhibition of calcium influx and the modulation of intracellular calcium movement.

Adenosine Triphosphate↗

PubMed1995

Skeletal muscle contraction modulates carbonic anhydrase phenotype in adult mouse dorsal root ganglion neurons.

Recently carbonic anhydrase (CA) activity was demonstrated in adult mammalian proprioceptive neurons of the lumbar dorsal root ganglion (DRG). To assess if neuron-target interactions govern the neuronal CA phenotype, we examined how various experimental procedures which modify the interactions of these neurons with their central and peripheral targets, affect mouse L5 lumbar DRG CA activity. In normal mice and under central disconnection, carbonic anhydrase activity was detected in 30% of neurons. One day after sciatic nerve transaction the percentage of CA-positive neurons decreased to around 50% of that in controls, although both the total number of neurons per ganglion and glial CA content were unchanged. The pattern of CA activity then remained stable until at least 30 days post-operative. All experimental procedures used to block muscle contraction, including ventral rhizotomy, tenotomy, local application to the nerve of both tetrodotoxin and lidocaine or intramuscular injection of the botulinum toxin, produced a significant decrease in neuronal CA staining. Moreover, axonal transport block by vinblastine induced a decrease in CA-positive neurons. These results show that functional neuron-muscle interactions independent of DRG-spinal Cord influences contribute to the regulation of CA activity in lumbar DRG neurons. This modulation could be under the control of unidentified activity-dependent molecular mechanism involving stimuli through the skeletal muscle contraction, inducing in turn, the synthesis of a CA-regulating factor(s) retrogradely transported to the neuronal cell body and/or nuclei.

Animals↗

PubMed1998

In vivo human knee joint dynamic properties as functions of muscle contraction and joint position.

Information on the dynamic properties (joint stiffness, viscosity and limb inertia) of the human knee joint is scarce in the literature, especially for actively contracting knee musculature. A joint driving device was developed to apply small-amplitude random perturbations to the human knee at several flexion angles with the subject maintaining various levels of muscle contraction. It was found that joint stiffness and viscosity increased with muscle contraction substantially, while limb inertia was constant. Stiffness produced by the quadriceps was highest at 30 degrees flexion and decreased with increasing or decreasing flexion angle, while knee flexors produced highest stiffness at 90 degree flexion. When knee flexion was < 60 degrees, stiffness produced by the quadriceps was higher than that of the hamstrings and gastrocnemius at the same level of background muscle torque, while knee flexor muscles produced higher stiffnesses than the quadriceps at 90 degree flexion. Similar but less obvious trends were observed for joint viscosity. Passive joint stiffness at full knee extension was significantly higher than in more flexed positions. Surprisingly, as the knee joint musculature changed from relaxed to contracting at 50% MVC, system damping ratio remained at about 0.2. This outcome potentially simplifies neuromuscular control of the knee joint. In contrast, the natural undamped frequency increased more than twofold, potentially making the knee joint respond more quickly to the central nervous system commands. The approach described here provides us with a potentially valuable tool to quantify in vivo dynamic properties of normal and pathological human knee joints.

Computer Simulation↗

PubMed1978

Modification of combined migraine-muscle contraction headaches using BVP and EMG feedback.

The effect of blood volume pulse (BVP) and frontalis muscle action potential (EMG) feedback on control of vasoconstriction of the temporal artery and frontalis muscle activity in combined migraine-muscle tension subjects was investigated in a multiple baseline design (across subjects and responses). The data indicated: (a) both subjects obtained an ability to control BVP during BVP feedback and EMG during EMG feedback; (b) there were decreases in frequency of migraine headaches during BVP feedback and decreases in muscle contraction headaches during EMG feedback. The results of this study supported the theoretical explanation of two pain mechanisms involved in combined muscle contraction-migraine headaches as well as the effectiveness of bio-feedback procedures that target directly the specific pain mechanism in the elimination of the two types of head pain.

Adult↗

PubMed1991

Recent neutron scattering studies of muscle contraction and its control.

We have presented two applications of the method of neutron scattering utilizing selective deuteration of actin. In these experiments the actin was rendered effectively invisible to neutrons by matching the scattering-length densities of deuterated actin and the solvent. The scattering of neutrons by myosin S1 and by Tm bound to this actin was studied. For free chymotrypsin-generated S1 it was found that Rg = 4.0 +/- 0.15 nm, while for papain-generated S1 it was found that Rg = 4.6 +/- 0.2 nm. Upon binding of papain-generated S1 to actin at low NS1/N actin ratios, the change in Rg in difference experiments was delta Rg = 0.05 +/- 0.15 nm. This lack of significant change in Rg in the very low-s domain confirms and extends our earlier neutron scattering work in the higher-s domain. The longest chords of S1, as well as shorter ones, are not significantly altered upon actin binding. These results indicate that muscle contraction does not occur as a result of large-scale changes in S1 structure. In actin-Tm complexes, a measurement of the mean cross-helix separation, d, of Tm molecules has been made using neutron scattering. With deuterated actin matched out in 93% D2O buffer, it was found that d = 7.9 +/- 0.3 nm. This value is in good agreement with a model based on Tm crystallography and also with recent electron microscopy results. These experiments demonstrate the feasibility and value of neutron diffraction and scattering techniques in the study of muscle contraction and its control. One can expect that the further employment of emerging cell biology techniques for generating deuterated proteins will aid our understanding of muscle in the future.

Actins↗

PubMed1980

The Croonian lecture, 1979: Regulation of muscle contraction.

In this lecture I review briefly the history of the recognition of calcium ion as the sole regulatory factor of muscle contraction at the molecular level and how this led to the discovery of the troponin-tropomyosin system, which is the regulatory system of striated muscles of almost all deuterostomias and some protostomias. This is followed by a brief comment on the myosin-linked regulation, which plays a dominating role in many protostomian muscles. The regulatory mechanism in vertebrate smooth muscle is then discussed; the view is advanced that the leiotonin-tropomyosin system may be the only regulatory device for this muscle. Ca-binding components of troponin and smooth muscles of vertebrates are compared with modulator protein, an omnipresent Ca-binding protein of very conservative nature throughout evolution. Finally, the modes of action of Ca ion in different kinds of cell motility are discussed from an evolutionary point of view.

Actins↗

PubMed1986

Role of substance P nerves in longitudinal smooth muscle contractions of the esophagus.

Longitudinal muscle strips from different sites along the opossum esophagus were stimulated transmurally so as to produce neurally mediated contractions. Low-frequency transmural stimulation produced contractions after termination of the stimulus ("off" contractions), whereas high-frequency stimuli produced contractions beginning during the stimulus and extending beyond termination of the stimulus (extended-duration contractions). The intrastimulus portion of the extended-duration contraction was partially antagonized by atropine or substance P desensitization, whereas the poststimulus portion of the contraction was selectively and fully antagonized by desensitization with substance P. A combination of atropine and substance P desensitization abolished the extended-duration contraction. The amplitude of contraction was greater in the proximal than in the distal strips, irrespective of the mode of stimulation. The poststimulus portion of the extended-duration contraction was significantly longer in muscle strips taken from more distal than proximal portions of the esophagus. This gradient in duration of contractions was abolished by substance P desensitization but was not affected by atropine. Exogenously applied substance P (10 microM) produced equally sustained long-duration contractions at all sites along the esophagus. These observations suggest that a) both acetylcholine- and substance P-containing nerves are responsible for the extended-duration contraction of longitudinal muscle, and b) transmural stimulation causes an aborally directed increase in the duration of contractions; this gradient of increasing duration of contraction appears to be due to a more prolonged neural release of substance P at more distal sites.

Animals↗

PubMed1994

Effects of clonidine on the reflex cardiovascular responses and release of substance P during muscle contraction.

The effects of microdialyzing clonidine into the L-7 dorsal horn on the cardiovascular responses, renal sympathetic nerve activity (RSNA), and release of substance P (SP) evoked by static contraction of the triceps surae muscle were studied using anesthetized cats. A microdialysis probe was inserted into the spinal cord ipsilateral to the muscle being contracted or stretched. Contraction, evoked by stimulation of the distal ends of the cut L-7 and S-1 ventral roots for 1 minute, increased mean arterial pressure (MAP), heart rate (HR), and RSNA by 48 +/- 6 mm Hg, 18 +/- 2 beats per minute, and 66 +/- 5%, respectively. Passive stretch of the same muscle for 1 minute also increased MAP, HR, and RSNA by 51 +/- 6 mm Hg, 17 +/- 2 beats per minute, and 50 +/- 3%, respectively. Microdialysis of clonidine (380 mumol/L) blunted the contraction-evoked responses: MAP, HR, and RSNA increased by 19 +/- 4 mm Hg, 7 +/- 1 beats per minute, and 24 +/- 5%, respectively. The increases elicited by passive stretch were also attenuated (MAP, 22 +/- 4 mm Hg; HR, 6 +/- 1 beats per minute; and RSNA, 15 +/- 4%). This attenuation by clonidine was dose dependent (3.8 mumol/L, 38 mumol/L, 380 mumol/L, and 3.8 mmol/L). Preadministration of the alpha 2-adrenergic antagonist yohimbine (3 mmol/L) blocked the effect of clonidine (380 mumol/L) on the cardiovascular and RSNA responses to muscle contraction. Clonidine (380 mumol/L) did not alter the release of SP in the dorsal horn during contraction (before clonidine, 0.380 +/- 0.018 fmol/100 microL; after clonidine, 0.356 +/- 0.012 fmol/100 microL).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

The fastest contracting muscles of nonmammalian vertebrates express only one isoform of the ryanodine receptor.

The skeletal muscles of chickens, frogs, and fish have been reported to express two isoforms (alpha and beta) of the sarcoplasmic reticulum calcium release channel (ryanodine receptor or RYR), while mammals express only one. We have studied patterns of RYR isoform expression in skeletal muscles from a variety of fish, reptiles, and birds with immunological techniques. Immunoblot analysis with a monoclonal antibody that recognizes both nonmammalian RYR isoforms and a polyclonal antibody specific to the alpha isoform show two key results: (a) two reptilian orders share with mammals the pattern of expressing only the alpha (skeletal) RYR isoform in skeletal muscle; and (b) certain functionally specialized muscles of fish and birds express only the alpha RYR isoforms. While both isoforms are expressed in the body musculature of fish and birds, the alpha isoform is expressed alone in extraocular muscles and swimbladder muscles. The appearance of the alpha RYR isoform alone in the extraocular muscles and a fast-contracting sonic muscle in fish (toadfish swimbladder muscle) provides evidence that this isoform is selectively expressed when rapid contraction is required. The functional and phylogenetic implications of expression of the alpha isoform alone are discussed in the context of the mechanism and evolution of excitation-contraction coupling.

Animals↗

PubMed1985

Can oligomeric myosin participate in smooth muscle contraction?

An experimental model was constructed to examine the possible fact that myosin oligomers take a part in smooth muscle contraction. Single fibres prepared from glycerinated rabbit skeletal muscle were emptied of myosin and then irrigated with purified chicken gizzard myosin. This was a good preparation in which to see the structural change of gizzard myosin and its interaction with actin filaments under the electron microscope. The structure of gizzard myosin was thoroughly changed by varying the concentration of free Mg2+ in the bathing solution. Myosin thick filaments were formed at the position of the A-band longitudinally bridging adjacent I-segments at high concentration of free Mg2+, while most of them disappeared from the A-band and some localized in the I-segment at low concentration of free Mg2+. When this preparation was induced to contract isometrically, it showed quite different sarcomere patterns at high and low concentrations of free Mg2+. Tensions developed by this preparation were of the same magnitude at high and low concentrations of free Mg2+, which were approximately 5% of that developed by glycerinated skeletal muscle fibres. The shortening of the prepared fibre in a contracting medium was almost the same at varying concentrations of free Mg2+. The relation between the structural organization and the contracting nature of the prepared fibre as the concentration of free Mg2+ was varied is discussed in this paper with respect to the significance of oligomeric myosin in smooth muscle contraction.

Animals↗

PubMed1985

Relationships between jaw pain and jaw muscle contraction level: underlying factors and treatment effectiveness.

EMG representations of jaw muscle contraction levels were measured in dental patients with TMJ problems in addition to history and physical evidence of bruxing and clenching, TMJ problems alone, bruxing and clenching, and no pain. Patients with TMJ problems plus bruxing/clenching had EMG levels similar to those with clenching and bruxing problems alone. These levels were far higher than those in the groups with similarly low TMJ problems alone and with no pain. The pain groups were normal for anxiety level and life stress. Although a third of the patients produced a conversion V pattern on the MMPI, no effect was seen on treatment effectiveness. All but a few of the mixed TMJ problem/bruxism/clenching patients and of the bruxism/clenching patients showed considerable reduction in pain through use of treatment oriented toward muscle tension awareness and relaxation. The group with TMJ problems and normal masseter muscle tension made little progress.

Anxiety↗

PubMed1985

Vibration and muscle contraction affect somatosensory evoked potentials.

We recorded potentials evoked by specific somatosensory stimuli over peripheral nerve, spinal cord, and cerebral cortex. Vibration attenuated spinal and cerebral potentials evoked by mixed nerve and muscle spindle stimulation; in one subject that was tested, there was no effect on cutaneous input. Presynaptic inhibition of Ia input in the spinal cord and muscle spindle receptor occupancy are probably the responsible mechanisms. In contrast, muscle contraction attenuated cerebral potentials to both cutaneous and muscle spindle afferent volleys; central mechanisms modulating neurons in the dorsal columns nuclei, thalamus, or cerebral cortex are probably responsible.

Achilles Tendon↗

PubMed1993

Muscle contraction and inward current induced by silver and effect of Ca2+ channel blockers.

Single fibers from toe or anterior tibialis muscle contracted transiently and then tonically in the presence of 1.8 mM Ca2+ on addition of 10 microM Ag+. Exposure of fibers to Cd2+ completely inhibited tonic contraction and modified phasic contraction to some extent. Nifedipine at 10 microM initially potentiated and then completely inhibited twitch tension; subsequently, fibers no longer contracted phasically in response to 20 microM Ag+, whereas slight tonic contraction still occurred. Fibers with membrane potential clamped at -90 mV produced maintained inward current on application of Ag+. Simultaneous administration of 1 mM Cd2+ and 10 microM Ag+ to fibers voltage clamped with the double mannitol gap technique almost completely blocked the inward current. Removal of Cd2+ elicited a rapid and large inward current. Ag(+)-induced inward current was inhibited when 1 mM Cd2+ was applied to fibers during development of the inward current. In fibers paralyzed with 10 microM nifedipine, the inward current induced by 10 microM Ag+ was partially inhibited. These results suggest that phasic contraction induced by Ag+ is controlled by L-type Ca2+ channels (probably voltage sensors) located in the T-tubular membrane, whereas tonic contraction involves Ca2+ channels sensitive and/or insensitive to dihydropyridine in the surface and T-tubular membranes.

Animals↗

PubMed1977

Return of myosin heads to thick filaments after muscle contraction.

The heads of myosin molecules, which move to the vicinity of the thin filaments to react with actin during muscle contraction, return to the thick filaments after contraction. The return occurs in two stages; a rapid return of the majority of the myosin heads is followed by a slow return of the rest.

Animals↗

PubMed2001

Greater movement-related cortical potential during human eccentric versus concentric muscle contractions.

Despite abundant evidence that different nervous system control strategies may exist for human concentric and eccentric muscle contractions, no data are available to indicate that the brain signal differs for eccentric versus concentric muscle actions. The purpose of this study was to evaluate electroencephalography (EEG)-derived movement-related cortical potential (MRCP) and to determine whether the level of MRCP-measured cortical activation differs between the two types of muscle activities. Eight healthy subjects performed 50 voluntary eccentric and 50 voluntary concentric elbow flexor contractions against a load equal to 10% body weight. Surface EEG signals from four scalp locations overlying sensorimotor-related cortical areas in the frontal and parietal lobes were measured along with kinetic and kinematic information from the muscle and joint. MRCP was derived from the EEG signals of the eccentric and concentric muscle contractions. Although the elbow flexor muscle activation (EMG) was lower during eccentric than concentric actions, the amplitude of two major MRCP components-one related to movement planning and execution and the other associated with feedback signals from the peripheral systems-was significantly greater for eccentric than for concentric actions. The MRCP onset time for the eccentric task occurred earlier than that for the concentric task. The greater cortical signal for eccentric muscle actions suggests that the brain probably plans and programs eccentric movements differently from concentric muscle tasks.

Adult↗

PubMed1995

Phosphorylation of dense-plaque proteins talin and paxillin during tracheal smooth muscle contraction.

Reorganization of cytoskeletal-membrane interactions during contractile stimulation may contribute to the regulation of airway smooth muscle contraction. We investigated the effect of contractile stimulation on the phosphorylation of the actin-membrane attachment proteins talin, vinculin, and paxillin. Stimulation of 32P-labeled canine tracheal smooth muscle strips with acetylcholine (ACh; 10(-3) M) resulted in a rapid 2.6-fold increase in phosphorylation of serine and/or threonine residues, compared with resting levels of 0.22 mol PO4(3-)/mol talin. After stimulation with ACh, phosphorylation of tyrosine residues on paxillin increased approximately threefold. Two-dimensional phosphopeptide mapping of in vivo labeled talin and paxillin indicated phosphorylation on a limited number of sites. Vinculin phosphorylation was undetectable in either resting or ACh-stimulated muscle. We conclude that phosphorylation of talin and paxillin occurs during ACh-stimulated contraction of tracheal smooth muscle and that distinct signaling pathways activate a serine/threonine kinase that phosphorylates talin and a tyrosine kinase that phosphorylates paxillin. The pharmacological activation of airway smooth muscle cells might involve the anchoring of contractile filaments to the membrane.

Acetylcholine↗

PubMed2006

The influence of taste on swallowing apnea, oral preparation time, and duration and amplitude of submental muscle contraction.

Prior research has documented a modulating effect of taste on swallowing. We hypothesized that presentation of tastant stimuli would be a significant variable in swallowing-respiratory coordination, duration of oral bolus preparation, and submental muscle contraction. Twenty-three healthy females were presented with 1-cm(3) gelatin samples flavored with 4 tastants of increasing intensities. Visual analogue scale ratings of perceived intensity of each were used to identify relative equivalent concentrations across the 4 tastants. Data were then collected during ingestion of 5 trials of the 4 equivalent tastants using measurements of nasal airflow and submental surface electromyography (sEMG) to record biomechanical measures. Chi-square analysis failed to identify a statistically significant influence of taste on the phase location of swallowing apnea. Repeated measures analysis of variance demonstrated significant taste effects for oral preparation time, submental sEMG amplitude, and duration (P < 0.02). Sweet tastants were prepared for a shorter time when compared with bitter tastants. Swallow duration for sour, salty, and bitter tastants were longer than sweet and neutral tastants. Sour tastants resulted in the greatest amplitude of submental muscle contraction during swallowing. This study supports existing research that found that sour substances were swallowed with more effort when compared with other tastes.

Adult↗

PubMed2000

Tension changes in the cat soleus muscle following slow stretch or shortening of the contracting muscle.

1. The permanent extra tension after a stretch and the deficit of tension after a shortening in the soleus muscle of the anaesthetised cat were measured using distributed nerve stimulation across five channels. At low rates of stimulation the optimum length for a contraction was several millimetres longer than that when higher rates of stimulation were used, so that movements applied over the same length range could be on the descending limb of the full activation curve but on the ascending limb of the submaximal activation curve. 2. The extra tension after stretch and the depression after shortening were present only near the peak and on the descending limb of the length-tension curve. Effects on final tension of changing the speed and amplitude of stretches or shortenings were found to be small. 3. Statistical analysis showed that variations in the tension excess or deficit due to changing stimulus rate could be entirely attributed to the effect of stimulus rate on the length-tension relation, as when length was expressed relative to optimum for each rate, stimulus rate was no longer a significant determinant of the tension excess or deficit. 4. The extra tension after stretch and the depression after shortening disappeared if stimulation was interrupted and tension briefly fell to zero. 5. These effects were explained in terms of a non-uniform distribution of sarcomere length changes at long muscle lengths. During stretch some sarcomeres are stretched to beyond overlap while others lengthen hardly at all. During shortening some sarcomeres shorten much further than others. 6. These mechanisms have important implications for exercise physiology and sports medicine.

Analysis of Variance↗