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Pentobarbitone and skeletal muscle contractions: on the interaction with the effect elicited by the beta-adrenoceptor agonist, terbutaline.

The soleus, a slow-contracting muscle, and the extensor digitorum longus (EDL), a fast-contracting muscle from guinea-pig were prepared for isometric recording in vitro. Subtetanic contractions were evoked by transmural field-stimulation. Pentobarbitone increased the force of contraction in both muscles. In the soleus it shifted the stimulation frequency-response curve to the left. Terbutaline caused a decrease in the force of subtetanic contractions of the soleus, an effect which was dependent on the stimulation frequency. In the presence of pentobarbitone, the stimulation frequency had to be lowered by about 2 HZ in order to maintain the optimum response to terbutaline. The EDL responded to terbutaline with an increased force of contraction. In this case the stimulation frequency was less critical and the effects were the same in the presence and in the absence of pentobarbitone. Experiments with alpha-chloralose yielded results similar to those obtained with pentobarbitone.

Animals

Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle.

Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction.

Actins

Early cellular changes and circular muscle contraction associated with the induction of decidualization by intrauterine oil in mice.

Intrauterine instillations of oil or saline distended the uterus in ovariectomized mice treated with progesterone + oestrogen to sensitize the uterus to a decidualizing stimulus. Saline does not induce decidualization, and therefore uterine distension per se is not the trigger to decidual induction. Oil induces decidualization, but does not involve gross damage to the epithelium, penetration of oil into the stroma or release of epithelial lipid into the stroma. Instillation (oil, saline or sham) induced a contraction of the circular muscles along the length of the uterus which closed the uterine lumen, expelled most of the oil and located the remainder primarily in the antimesometrial cleft of the lumen. Progesterone inhibited longitudinal muscle contraction and facilitated circular muscle contraction. These effects are discussed in relation to the spacing and implantation of blastocysts.

Animals

Electrical and mechanical activities of longitudinal muscle contraction elicited by transmural electric stimulation.

Intracellular electrical and mechanical activities were simultaneously recorded from the longitudinal muscle of isolated guinea-pig jejunum when the preparation was stimulated transmurally by square pulses of 1 msec, 10 Hz, 10-40 V. Transmural stimulation of more than 30 V induced co-ordinated peristaltic waves under intraluminal pressure at levels subthreshold for the peristaltic reflex. Transmural stimulation of less than 30 V induced various types of mechanical responses. After termination of stimulation, rebound excitation was observed. Electrical activities of the longitudinal muscle were compared with various mechanical responses. Slow depolarization without spike potential was recorded when the longitudinal muscle contracted without circular muscle contraction. However, spike potential was recorded from the longitudinal muscle when circular muscle contraction was present as a response. Hyperpolarization was observed soon after the beginning of stimulation. This hyperpolarization was persistent to atropine at 10(-6) g/ml. These electrical and mechanical responses to transmural stimulation disappeared when the preparation was treated with tetrodotoxin at 2 X 10(-7) g/ml.

Animals

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

Effects of muscle contraction and of adenosine on capillary transport and microvascular flow in dog skeletal muscle.

The postarteriolar response of capillary transport and microvascular flow distribution to muscle contraction and to adenosine was measured by the indicator dilution technique in isolated dog gracilis muscles perfused with blood at controlled flows. A model of dual circulation was used to analyze the partition of microvascular flow. The extraction (E) of 125I-iodoantipyrine (IAp) served as an indicator of capillary flow whereas the capillary transport capacity coefficient (PSc) of 22Na was used to assess the changes in capillary surface area available for exchange. Muslce contraction produced by electrical stimulation of the motor nerve increased mean E-IAp from 0.94 +/- 0.03 (sd) to 0.95 +/- 0.01 and produced a 2.0- to 2.9-fold increase in PSc-Na. Intra-arterial adenosine produced results similar to those caused by muscle contraction. We conclude that (1) in resting muscle, most of the flow circulates through exchanging blood vessels and (2) in addition to the primary mechanisms of arteriolar vasodilatation, a substantial increase in the number of capillaries available for exchange of materials plays an important role in the adaptive response to increased metabolic demand.

Adenosine

The responses of human muscle spindle endings to vibration of non-contracting muscles.

1. In micro-electrode recordings from the human peroneal and tibial nerves, the responses of thirty-two primary spindle endings, thirteen secondary spindle endings and three Golgi tendon organs were studied during vibration of the tendons of the receptor-bearing muscles in the leg. The amplitude of the applied vibration was 1-5 mm and the frequency was varied from 20 to 220 Hz. As checked with e.m.g. and torque measurements, the muscles of the leg were relaxed during the sequences analysed. 2. Providing that the vibrator was accurately applied, all endings responded with discharges phase-locked to the vibration cycles, the discharge rates being at the vibration frequency or at subharmonics of that frequency. The response to vibration was of abrupt onset and offset, was maintained for the duration of vibration, and was not subject to fluctuation with changes in attention or with remote muscle contraction. 3. The maximal discharge rate that could be achieved varied from one ending to the next, and increased with the length of the receptor-bearing muscle. For endings driven at their maximal rate an increase in vibration frequency produced a decrease in discharge rates as the ending changed to a subharmonic pattern of response. The converse occurred on decreasing vibration frequency. 4. For any given muscle length, primary endings could generally be driven to higher rates than secondary endings but there was a wide range of responsiveness within each group and a significant overlap between the groups. At medium muscle length, the most responsive primary endings could be driven up to 220 Hz but secondary endings did not reach discharge rates higher than 100 Hz. 5. With combined vibration and passive movements, primary endings exhibited maximal vibration responsiveness during the stretching phases, sometimes firing twice per vibration cycle. During the shortening phases, however, they usually ceased responding to the vibratory stimulus. The vibration responsiveness of secondary endings was not potentiated to the same extent by on-going muscle stretch or reduced to the same extent by on-going muscle shortening. Thus, during shortening, secondary endings may be more responsive than primary endings. 6. The responses of primary endings to tendon taps were reduced during muscle vibration, a reduction which probably contributes to vibration-induced suppression of tendon jerks. Additionally, as the muscle shortened after tendon percussion, there was a transient pause in the response to vibration.

Action Potentials

Cyclic nucleotide levels during carbachol-induced smooth muscle contractions.

Cyclic nucleotide levels and tension were measured at various times during carbachol-induced smooth muscle contractions. Cyclic GMP levels were markedly increased during contractions of rat vas deferens, guinea pig myometrium and guinea pig taenia coli, but were unchanged during contractions of rat uterus or guinea pig ileum. No significant changes in cyclic GMP levels could be detected in estrogen-primed rat uteri at any of the times or drug concentrations studied. Even in tissues in which large increases in cyclic GMP levels could be detected during carbachol-induced contractions (i.e. guinea pig myometrium and taenia coli) the contractions appeared to precede the cyclic GMP increases by several seconds. No significant changes in cyclic AMP levels were observed during carbachol-induced contractions in any of the smooth muscles studied. Thus, changes in tissue levels of the cyclic nucleotides do not appear to be responsible for the initiation of carbachol-induced smooth muscle contractions.

Animals

Arachidonic acid is responsible for the smooth muscle-contracting activity of G-acid.

G-acid, a smooth-muscle-contracting substance isolated from human blood plasma, was previously identified as 3-octadecenoic acid. Synthetic cis- and trans-3-octadecenoic acid, however, are biologically inactive. G-acid actually consists of a mixture of fatty acids, characteristic of animal tissues. The biological activity is caused by arachidonic acid, which contracts smooth muscle upon in situ conversion to prostaglandins.

Animals

Behavioral intervention with muscle-contraction headache: a review.

Studies involving behavioral intervention with muscle-contraction headache are reviewed. Intervention approaches have most frequently involved frontal electromyographic feedback and relaxation instructions. Although behavioral intervention packages have been more effective than control procedures in reducing headache activity, identification of active components of these packages is difficult. Specifically,, the contribution of placebo, expectancy and demand factors, reactive effects of self-monitoring, and home practice have not been adequately assessed. The importance of assessing individual differences in etiology and in response to intervention is stressed. The results of some studies are congruent with the hypothesized muscle tension etiology of muscle-contraction headaches but the results from others suggest that factors other than muscle-tension may be involved. Supportive laboratory research on the intervention procedures and cost-efficiency of electromyographic feedback and relaxation instructions are discussed.

Attitude

Controlled trial of EMG feedback in muscle contraction headache.

Twenty-eight patients suffering from severe, longstanding muscle contraction headache were randomly assigned to two groups, one receiving electromyographic (EMG) feedback therapy and the other, "most suitable alternative therapy." Headache intensity and severity as well as drug intake were reduced in the feedback group (p less than or equal to 0.01) as opposed to no improvement in the control group. The positive treatment effect in the feedback group persisted through a three-month follow-up period. EMG feedback therapy is effective in the treatment of muscle contraction headache even in its chronic, severe form, which is resistant to traditional treatment methods.

Adult

Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig.

The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed.

Albuterol

Equatorial x-ray reflections from contracting muscle after an applied stretch.

The equatorial X-ray reflections were recorded from contracting muscle after a slow stretch. The intensity ratio of the 1,0 to the 1,1 reflections (I10/I11) after the stretch was not significantly different from that during an isometric tetanus at the same sarcomere length, although the tension after the stretch was considerably greater than isometric. This suggests that an almost identical number of cross-bridges produce a greater tension after a slow stretch than during an isometric tetanus.

Animals

Signaling mechanisms of vasopressin/oxytocin-type neuropeptide-induced muscle contraction in the sea cucumber Apostichopus japonicus.

The myoregulatory action of vasopressin/oxytocin (VP/OT)-type neuropeptides is evolutionarily conserved across Bilateria. In vertebrates, the signaling cascades involved have been comprehensively characterized in several muscle types, including uterine and gastrointestinal smooth muscles. VP/OT-type neuropeptide-induced muscle contraction or relaxation has been reported in a variety of invertebrates, but the downstream signaling pathways responsible for these effects have yet to be elucidated. Here, using heterologous cell systems and in vitro pharmacological experiments, we investigated the signaling pathways underlying VP/OT-type neuropeptide (holotocin) induced contraction of the longitudinal muscle of the body wall (LMBW) in the sea cucumber Apostichopus japonicus (phylum Echinodermata), a deuterostome invertebrate. Holotocin-induced contraction of the LMBW comprised two distinct phases: an initial rapid phasic contraction followed by a sustained tonic contraction. Pharmacological experiments revealed that upon binding to its receptor AjHOR, holotocin activates a Gαq-dependent pathway, leading to phospholipase C (PLC) activation and subsequent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers Ca2+ release from intracellular Ca2+ stores via IP₃ receptors (IP3R), but depletion of intracellular Ca2+ does not activate store-operated Ca2+ entry (SOCE). DAG activates protein kinase C (PKC), which may modulate the activity of ion channels in the plasma membrane, resulting in membrane depolarization, opening of voltage-gated Ca2+ channels (VGCCs), and subsequent influx of extracellular Ca2+. Overall, this study reveals similarities and differences in the signaling pathways mediating smooth muscle contraction in invertebrates and vertebrates, providing new insights into the evolution of these mechanisms across the Bilateria.

Ca(2+)

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