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At least 19 recordsLinked to original sources

Caffeine contracture in transverse tubules-disrupted fiber and effect of anomalous anions on the contracture in frog twitch fiber.

Caffeine contracture in transverse tubules-disrupted (T-disrupted) muscle preparation and the effect of anomalous anions (SCN and NO3) on the contracture in single twitch fibers or thin bundles consisting of 2 or 3 fibers of frog were investigated. The magnitude and the rate of rise of caffeine contracture tension were decreased by T-disruption and the decrease was more marked at lower concentrations of caffeine. No seasonal difference between summer and winter frogs on the effect of T-disruption on caffeine contracture was observed. On the other hand, the magnitude and the rate of rise of caffeine contracture tension in the intact preparation was increased by anomalous anions, whereas the rate of spontaneous relaxation of the contracture was decreased. The effect of SCN on caffeine contracture appeared 5 min after the pre-exposure of muscle preparation of SCN-Ringer solution, with the maximal effect appearing after 10 min. The threshold curve of caffeine contracture was shifted toward the lower caffeine concentrations by anomalous anions and the extent of the shift in the curve was more pronounced with SCN than with NO2. In contrast, the potentiating effect of these anions on the caffeine contracture completely disappeared in T-disrupted muscle preparation. On the basis of these results, the caffeine pathway to the sarcoplasmic reticulum, and the sites and mechanism of the action of anomalous anions on caffeine contracture are discussed.

Animals

The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration.

Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture.

Animals

[Influence of homologous n-alcanoic acids on the function properties of isolated skeletal muscles. III. Contractures by fatty acids and relations to the effects of caffeine].

The influences of octanoic, decanoic, and hexadencanoic acid were tested on the contracture capability of isolated skeletal muscle of frogs and rats. 1. 100 mM octanoic or 10mM decanoic acid induce contractures in skeletal mucles after 20-30 min of exposure. 2. The time of exposure necessary for induction of contractures is shortened by an increase of bath temperature, electrical stimulation or KCl-depolarization of muscles. 3. Simultaneous addition of fatty acid and caffeine (10 mM) effects a depression and a delay of the caffeine contracture. The contractures evoked by 5 mM caffeine are inhibited by lower concentrations of fatty acids (1 mM octaonoic acid, 0,1 mM hexadecanoic acid). 4. After the complete development of a caffeine (or fatty acid) contracture the muscle is not able to develop an identical contracture by a second application of the same drug, even after intermediate treatment during one or two hours in Ringer solution. If the contracture is interrupted one minute after the caffeine application by changing the solution, the tension returns quickly to the resting level. A subsequent addition of caffeine (10 mM) after about 10 minutes effects an identical contracture. Thus the effect of fatty acids on caffeine contracture may be studied on the same muscle which served as its own control. 5. As mechanisms involved in the development of fatty acid contractures and in the inhibition of caffeine contractures, interactions of free fatty acids and lipids of biological membranes are disucssed. Especially, there may be changes of the calcium affinity of cellular membranes.

Animals

Effect of SCN on potassium contracture in twitch muscle fibers of the frog.

The effect of SCN on potassium contracture, especially the time course and the mechanical inactivation of the contracture, was investigated using frog twitch muscle fibers. SCN increased the magnitude and the rate of rise of the potassium contracture tension and prolonged its time course. These effects of SCN depended on the concentration of K+ in the external medium and on the duration of pretreatment of the fibers with SCN-Ringer solution. The potentiating effect of SCN on the potassium contracture tension was pronounced at lower and moderate concentrations of K+ and this effect attained a maximum within 1 min after the pretreatment. In the contracture induced by exposure of the fibers to K-SCN-solution without the pretreatment, the time course of the contracture, especially the retardation of the spontaneous relaxation, was marked at higher concentrations of K+. This retarding effect of SCN attained a maximum at more than 10 min after the pretreatment with SCN-Ringer solution. SCN shifted the mechanical inactivation curve of potassium contracture toward lower concentrations of K+, as in the case of the activation curve, and markedly increased the rate of the inactivation induced by conditioning with 15 mM K+. In addition, SCN delayed the recovery of potassium contracture from the mechanical inactivation induced by preceding K-SCN-contracture. On the basis of these results, the sites and the mechanism of action of SCN on potassium contracture are discussed.

Animals

Reversible Inhibition of Potassium Contractures by optical isomers of verapamil and D 600 on slow muscle fibres of the frog.

Potassium-induced contractures were measured isometrically in slow fibres of gastrocnemius muscle from the frog Leptodactylus ocellatus. Optical isomers of verapamil and of D 600 decreased the tension of K-contractures with the following characteristics: 1. 90 min exposures of the muscles to the (-)isomers of the drugs were more effective in decreasing tension of 40 mM KCl-contractures when successive challenges to 40 mM KCl were made each 10-15 min than without challenges during the incubation time. 2. In contrast to the depressing effect of (-)isomers of verapamil and D 600, the decrease of K-contractures by 1 mM EGTA in "Ca-free" solutions was independent on the history of 40 mM KCl-contractures. 3. The threshold concentration of K to cause contractures was the lower the lower the Ca-concentration. This relationship was little affected by (-)verapamil at concentrations of the drug which depressed by 50% the tension of 40 mM KCl-contractures in 1.8 mM CaCl2. 4. Verapamil and its methoxy-derivative D 600 were equipotent in depressing 40 mM KCl-contractures. Their optical (-)isomers were 4 to 5 times more potent than their corresponding (+)isomers. 5. K-tension curves in the presence of 6.1 muM (-)verapamil in 1.8 mM CaCl2 were similar to curves in 0.18 mM CaCl2 without the drug. 6. K-tension curves in 10 mM CaCl2 were shifted by (-)verapamil in nearly parallel manner towards higher K-concentrations. 7. The stereoselective decrease of K-contractures by verapamil and D 600 may be due to blockade of inward Ca-flux and to retardation of the reavailability of Ca2+ for release during partial depolarizations with K.

Animals

The effect of temperature on potassium chloride contracture in cat myocardium.

1. Contracture was induced in cat myocardium by exposure to 140 mM-KC1 In isotonic Tyrode solution. Force of contracture expressed as mg/mm2 (muscle cross-sectional area) falls with increasing cross-sectional area. 2. The effect of temperature on isometric force developed during contracture was evaluated both in normal (untreated) atrial and ventricular muscle and following treatment with sympatholytic drugs. 3. The force of contracture was not significantly affected by sympatholytic drugs at 36 degrees C. 4. In normal atrial and ventricular muscle, force of contracture decreased when the muscle was cooled from 36 to either 29 or 20 degrees C. 5. In atrial muscle, the effect of temperature was not changed by sympatholytic drugs. In contrast, exposure to sympatholytic drugs increased contracture force developed by ventricular muscle at 20 degrees C. Also, contracture force was significantly greater at 20 than at 36 degrees C in ventricular muscle from reserpine-pretreated cats. 6. It is suggested that ventricular muscle becomes more sensitive to the relaxing effects of endogenous catecholamines at temperature is lowered. 7. The differences shown between atrial and ventricular muscle with respect to the effect of temperature and sympatholytic drugs on contracture force may result from the differing amounts of sarcoplasmic reticulum found in these types of cardiac muscle and also from different mechanisms of "excitation-contracture" coupling in atrial and ventricular muscle.

Animals

An insight into Dupuytren's contracture.

Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.

Capillaries

Separate sites for the dantrolene-induced inhibition of contracture of the rat diaphragm preparation due to depolarization or to caffeine.

Addition of dantrolene 8.5 x 10(-5) M caused a mono-exponential decay of the depolarization contractures caused by inhibition of the sarcolemmal Na,K-ATPase with propranolol 1 mM or by depolarization of the sarcolemma and T tubular membranes with KCl 100 mM. The half-times of the inhibitory effects were 6 s for the propranolol contracture and 11 s for the KCl contracture. The inhibition of both contractures was complete. Inhibition of the caffeine (10 mM) contracture was bi-exponential with half-times of 45 s and 9.5 min. Inhibition was incomplete; 29.6 +/- 5.0% of the contracture tension could not be inhibited. The inhibition of twitch contractions was similar to that of the caffeine contracture, with half-times of 48 s and 9.1 min, and 20.6 +/- 1.2% of the initial twitch tension could not be inhibited. The contracture tensions induced by release of Ca from the mitochondria with dicumarol, and by actin-myosin binding with the sulfhydryl inhibitor, N-ethyl-maleimide, could not be inhibited by dantrolene. The present results indicate that dantrolene inhibits depolarization signals from the sarcolemma and the T tubular membranes, in addition to inhibition of the coupling between the T tubules and the sarcoplasmic reticulum, and of the release of Ca from the sarcoplasmic reticulum. All these effects of dantrolene may contribute to its therapeutic effect in malignant hyperthermia.

Animals

Contractures elicited by tetraethylammonium in avian muscle treated with methohexitone.

1 The chick biventer cervicis muscle immersed in methohexitone (8.8 x 10(-5) M) responded to tetraethylammonium with contractures which were dose-related. The ED50 for tetraethylammonium was 2.1 x 10(-3) M. 2 In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations: these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres. 3 The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation. 4 Tubocurarine (1.2 x 10(-6) M) displaced the dose-response curve for tetraethylammonium-methohexitone-induced contractures to the right. The dose-ratio was 15.63 +/- 1.98. 5 Physostigmine (1.8 x 10(-6) M) potentiated the activity of tetraethylammonium-methohexitone 3.26 or 3.84 fold, depending on the method of calculation used. 6 Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium-methohexitone. 7 It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor.

Animals

Mitochondrial and sarcolemmal Ca2+ transport reduce [Ca2+]i during caffeine contractures in rabbit cardiac myocytes.

1. Contraction and intracellular Ca2+ (Ca2+i) transients were measured in isolated rabbit ventricular myocytes during twitches and contractures induced by rapid application of 10 mM-caffeine. 2. The amplitude of caffeine-induced contractures and the accompanying Ca2+i transients were larger than during normal twitches and also declined more slowly. This may be because only a fraction of sarcoplasmic reticulum (SR) Ca2+ is released during a normal twitch, or because of a temporal overlap of SR Ca2+ release and uptake during the twitch. 3. When a caffeine contracture was initiated in Na(+)-free, Ca(2+)-free medium (to prevent sarcolemmal Na(+)-Ca2+ exchange) the contracture and Ca2+i transient were larger and decreased much more slowly. Thus, Ca2+ extrusion via Na(+)-Ca2+ exchange may limit the amplitude of caffeine-induced contractures. 4. Relaxation half-time (t1/2) for the twitch (0.17 +/- 0.03 s) was increased to 0.54 +/- 0.07 s for caffeine contractures in control solution and 8.8 +/- 1 s for caffeine-induced contractures in Na(+)-free, Ca(2+)-free solution. These results confirm that the SR Ca2+ pump and Na(+)-Ca2+ exchange are the predominant mechanisms for cytoplasmic Ca2+ removal during relaxation. However slower mechanisms can still reduce intracellular [Ca2+]. 5. Relaxation of caffeine contractures in Na(+)-free solution was further slowed when (a) mitochondrial Ca2+ uptake was inhibited with the oxidative phosphorylation uncoupler, FCCP (t1/2 = 19.7 +/- 3.2 s), or (b) the sarcolemmal Ca(2+)-ATPase pumping ability was depressed by a large transmembrane [Ca2+] gradient (t1/2 = 27.5 +/- 6.9 s). 6. When the four Ca2+ transport systems were simultaneously inhibited (i.e. SR Ca2+ pump, Na(+)-Ca2+ exchange, mitochondrial Ca2+ uptake and sarcolemmal Ca2+ pump), relaxation was practically abolished, but the cell could recover quickly when Na+ was reintroduced and caffeine removed. 7. We conclude that, under our experimental conditions, the sarcolemmal Ca2+ pump and mitochondria are approximately 37- and 50-fold slower than the Na(+)-Ca2+ exchange at removing Ca2+ from the cytoplasm. Additionally, the SR Ca2+ pump is about 3-4 times faster than Na(+)-Ca2+ exchange.

Animals

BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers.

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.

Adenosine Triphosphate

[Comparative characteristics of depolarization (potassium) and acetylcholine contracture of Lampetra fluviatilis lamprey phasic muscle].

Acetylcholine (Ach) contractures of thin bundle from m. longitudinal linguae of the lamprey differs by several parameters from depolarization (potassium) contracture, although Ach similar to K ions totally depolarizes the surface membrane of muscle fibers. Maximum tension of Ach contracture is 30--100% higher than that of K contracture, maximum of both contractures being observed at the same membrane potential level (approximately -10mV). The rate of rise of Ach contracture is 10 times higher, whereas the latent period is 3 times shorter as compared with the same parameters of K contracture. At higher Ach concentrations (10(-5)--10(-4) g/ml) the latent period of contracture is shorter than that of depolarization.

Acetylcholine

Fibrous contracture of muscles following intramuscular injections in adults.

Periarticular fibrous muscle contractures in adults from repeated injections in the same site is predictable. The causes of joint contracture in children are many and complex, but in adults it seems certain that this phenomenon is the result of repeated injections of analgesics or other agents into 1 muscle area. Any drug if repeatedly injected locally may cause fibrosis of the muscle and subsequent joint contracture. Five cases of bilateral abduction contracture of the shoulder in adults including the first case of bilateral abduction contractures of shoulder and hip plus bilateral flexion contracture of elbow and extension contracture of a knee are reported. No underlying disease which might predispose to this fibrosis of muscles was noted. The frequency and period of injections were variable over several years. In all patients the interference in activtities of daily living were serious, but the deformities were corrected by release of the fibrous band with relief of discomfort and restoration of joint motion without recurrence. Noting the potential complication of repeated intramuscular injections in one area, this practice should be avoided whenever possible in adults, as well as in children.

Adult

Recovery of ultrastructural changes accompanying caffeine contractures in isolated muscle fibres of the crayfish.

Reversible caffeine contractures in isolated muscle fibres of the crayfish (Astacus fluviatilis; m. extensor carpopoditi) are accompanied by swelling of the diadic cisternae of the sarcoplasmic reticulum and by constriction of the T-system tubules. The membranes of the tubules may coalesce and form pentalaminar structures. These changes in the diadic region can be found already in fibres fixed 10 s after the sudden introduction of 4 mM or 6 mM caffeine solution. The changes are completely reversible. The recovery period after a 6 mM caffeine contracture lasts 20 min. The restitution of ultrastructural changes induced by caffeine correlates well with the recovery of responsiveness to a repeated application of caffeine. The pretreatment of fibres with procaine prevents both the generation of caffeine contractures and the occurrence of changes in the ultrastructure. No changes or a very slight enlargement of diadic cisternae were found during potassium contractures of comparable size and duration to caffeine contractures. The effect of procaine as well as the restitution of ultrastructural changes after the recovery of responsiveness to caffeine support the view that the cisternal swelling is a direct consequence of the calcium releasing action of caffeine. Isolated swelling of diadic cisternae and the absence of any changes in the remaining parts of the sarcoplasmic reticulum during reversible caffeine contractures could point to the existence of functional differentiation of the respective parts of the sarcoplasmic reticulum. The absence of ultrastructural changes during potassium contractures might indicate a different source of the activating calcium for contraction and/or a different mechanism of its release.

Animals

Physostigmine-induced contractures in frog skeletal muscle.

Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base.

Animals

Prenylamine-induced contracture of frog skeletal muscle.

1. Experiments were performed to determine the influence of prenylamine on excitation-contraction coupling in frog sartorius muscle. 2. Prenylamine (0.2-1.0 mM) produced a biphasic contracture in skeletal muscle characterized by an initial phasic and subsequent tonic contracture. 3. Neither dantrolene nor procaine blocked the prenylamine-induced contracture. Pretreatment with 100 mM K+ blocked the phasic but not the tonic component of the prenylamine contracture. 4. Prenylamine produced a sustained increase in 45Ca efflux at all concentrations that produce contracture. These concentrations of prenylamine also depressed the action potential, muscle twitch and resting potential. 5. Low concentrations of prenylamine (0.05 mM) which produced neither contracture, 45Ca efflux nor 45Ca influx, depressed the action potential, muscle twitch and K+ contracture. 6. The results suggest that prenylamine not only alters calcium mobility but also membrane permeability to other ions.

Action Potentials