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PubMed1993

Veratrine-induced tetanic contracture of the rat isolated left atrium. Evidence for novel direct protective effects of prazosin and WB4101.

An investigation has been made of the putative direct myocardial protective effects of the alpha 1-adrenoceptor antagonists, prazosin and WB4101, against tetanic contractures of rat isolated left atria following modified Na+ channel function and consequent Ca2+ loading elicited by veratrine. Veratrine evoked concentration-dependent, reversible, tetanic contractures which were critically dependent upon the external Ca2+ concentration. Tetrodotoxin (TTX), prazosin, WB 4101 and R 56865 (0.1-10 microM) prevented tetanic contracture elicited by veratrine (100 micrograms/ml) at concentrations which were significantly lower than those which decreased active tension development. The apparent Hill coefficients (nH) obtained for TTX, prazosin, WB 4101 and R 56865 were comparable (range 0.79-0.93), and are consistent with a single site of action. In contrast, the class 1 antiarrhythmic agents, quinidine and lidocaine, elicited no significant inhibition of veratrine-induced contracture at 30 microM, but almost completely abolished the contractures at 100 microM. The nH values for quinidine and lidocaine were found to be significantly greater than unity (3.1 and 2.6, respectively). The L-type Ca2+ channel blockers, diltiazem, nicardipine, nifedipine and verapamil only weakly prevented tetanic contracture, whilst markedly, and concentration-dependently, decreasing active tension development. Neither atropine (10 microM) nor propranolol (1 microM) significantly modified either veratrine-induced contractures or active tension development. In conclusion, evidence is presented of novel, direct protective effects of prazosin and WB 4101 against tetanic contracture following modified Na+ channel function and Ca2+ loading provoked by veratrine. The precise mechanisms involved are unclear at present, but appear to be distinct from blockade of atrial alpha 1-adrenoceptors or L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1981

Contractures in normal and denervated inferior oblique muscle of the rabbit.

Isometric contracture responses of normal and denervated inferior oblique muscles (IO) of the rabbit have been investigated in vitro at 35 degrees C. The threshold concentration for eliciting potassium contractures was about 20 mM K+. In normal IU low potassium concentrations up to about 50 mM K+ evoked only sustained contractures, higher concentrations were responded by contractures with an initial transient component. The transient tension development was maximal at about 100 mM K+ the sustained component at 80 mM K+. After denervation the characteristic time course of the contractures was not changed, but the tension output of the preparation was diminished and long-term denervated IO have a somewhat lowered threshold. In normal IO acetylcholine (ACh), succinylcholine (SCh) and choline (Ch) caused also sustained contractures, the threshold doses were about 5 microM for ACh and SCh and 500 microM for Ch. The ACh sensitivity of the preparations was increased by physostigmine and decreased or abolished by d-tubocurarine. Denervation increased the drug sensitivity but the shape of the contractures was hardly influenced. The properties of slow tonic muscle fibres in mammalian extraocular muscles (EOM) probably responsible for sustained contractures and their changes after denervation are discussed.

Acetylcholine↗
PubMed1981

Nickel substitution for calcium and the time course of potassium contractures of single muscle fibres.

In the virtual absence of external calcium (10(-9) M), peak tension of potassium contractures is not affected but their time course is markedly reduced. At 22 degrees C, the tension-time integral (area) of K+-contractures is reduced to about half its normal value. A similar reduction in the area of K+-contractures is observed when [Ca2+]0 is reduced to about 100 muM or less. When nickel substitutes for external calcium, K+-contractures present a normal time-course. Since nickel has been shown not to interact with contractile proteins these results indicate that extracellular calcium is apparently not directly participating in contractile activation nor in sustaining the time course of K+-contractures. External calcium deprivation affects also other phenomena related to excitation contraction coupling (ECC), such as the isometric tension-voltage relationship, the time course and extent of contractile repriming after a test contracture, the steady-state inactivation curve, and the capacity to sustain multiple contractures. Some of these effects indicate that external calcium may have a regulatory role on ECC phenomena. Nickel is an effective substitute for calcium in all these phenomena. The numerous contractures that a fibre can develop in the absence of calcium (nickel-substituted) indicate that the sarcoplasmic reticulum has either a large store of contractile activator, or a large recycling capacity.

Amphibians↗
PubMedDate not supplied

The relationship between ischemic contracture and no-reflow phenomenon in isolated rat heart.

The relationship between ischemic contracture and no-reflow phenomenon was studied in 59 isolated rat hearts during global ischemia. The contracture was measured by a water-filled balloon catheter placed in the left ventricular lumen. The time of onset of contracture was changed by preischemic infusion with buffer containing 0.5 mmoles/l iodoacetate (IAA) in order to get early contracture, and by hypothermia which delayed the development of contracture. The first signs of contracture were noticed in normothermia (37 degrees C) at 11 minutes, in hypothermia (26 degrees C) at 25 minutes, and in the IAA-infused group at 3 minutes. The completion of contracture occurred in these groups at 25, 90 and 11 minutes, respectively. The myocardial perfusability was tested at the pre- and postcontracture state by infusing 0.1% fluorescein in isotonic saline into the cannulated aortic root. The myocardial area perfused with fluorescein was quantified in colour photographs taken under ultraviolet light of frozen whole-heart sections. The myocardial perfusion - expressed ad percent of myocardial area - was 99% at the precontracture state in normothermia, 95% in hypothermia and 100% in the IAA-infused group. At the postcontracture state, the myocardial perfusion in these groups was 80, 56 and 18%, respectively. It was concluded that the no-reflow phenomenon in isolated rat heart is closely associated with the development of myocardial contracture during global ischemia.

Animals↗
PubMed2000

Delayed contractures induced by external cadmium ions in rat soleus muscle fibres.

Cd(2+)-induced contractures began with a delay of approximately =4 min after adding 3 mM Cd2+ to external solutions that contained Cl- as the major anion. Tension increased to approximately =20% of peak tetanic tension after 30 min and was maintained after Cd2+ washout. Tension developed more rapidly at higher [Cd2+] (up to 10 mM). There was a lack of correlation between the delay before the contracture and contracture tension: (1) tension was reduced by 2 mM CO2+ or 50 microM nifedipine, although the delay remained at approximately =4 min, and (2) the delay fell to seconds when Cd2+ was added in SO42- solutions, although tension was the same as in Cl- solutions. Since (SO4)2- solutions swell T-tubules, Cd2+ may enter the T-system before inducing contractures. Cd(2+)-induced contractures depended on external [Ca2+] since they were reduced when Ca2+ was omitted from solutions. The contractures did not depend on activation of excitation-contraction coupling, since tension was not altered when the voltage sensor was inactivated by depolarization in 40 mM K+. A small contracture developed with 3 mM Zn2+, but not 3 mM Co2+ or La3+. Both Cd2+ and Zn2+ activated the contractile proteins in skinned fibres. Cd(2+)-induced contractures may depend on external Cd2+ releasing Ca2+ from the sarcoplasmic reticulum (SR), or on Cd2+ entering the fibre, releasing Ca2+ from the SR and/or directly activating the contractile proteins.

Animals↗
PubMed1995

Role of the sodium-calcium exchange mechanism and the effect of magnesium on sodium-free and high-potassium contractures in pregnant human myometrium.

OBJECTIVE: Periodic uterine relaxation in labor relieves the fetus from hypoxia related to sustained contractions. A reduction in intracellular calcium is essential for relaxation. Therefore we aimed to clarify the extrusion mechanisms of intracellular calcium ions in pregnant human myometrium. STUDY DESIGN: Isometric contraction of small muscle bundles obtained from human myometrium at term was recorded. High-potassium and sodium-free solutions could induce stable contractures that revealed initial phasic contractions followed by tonic contractions. The effects of external calcium, external magnesium, nifedipine, and calcium adenosine triphosphatase inhibitors on both contractures were then examined. RESULTS: Because maximum tonic contraction was induced by 48 mmol/L potassium, this concentration was used. Both contractures depended on external calcium concentrations. Nifedipine, 10(-7) mol/L inhibited both initial phasic contractions and the tonic phase of the high-potassium contracture; however, it could not suppress the tonic phase of the sodium-free contracture. Calcium adenosine triphosphatase inhibitors, cyclopiazonic acid and lauryl sulfate, potentiated the tensions of tonic phases in both contractures; the effect of lauryl sulfate was stronger than that of cyclopiazonic acid. When external magnesium was gradually increased (from 0 to 9.6 mmol/L), both phasic contractions and the tonic phase of the high-potassium contracture transiently increased, followed by a reduction of tension, whereas the tonic phase of the sodium-free contracture was markedly inhibited by magnesium in a dose-dependent manner. CONCLUSION: The presence of the sodium-calcium exchange mechanism and the specific inhibitory effect of magnesium were indicated in human myometrium during pregnancy. These mechanisms might prevent the long tonic contractions, to protect the fetus from hypoxia during pregnancy and parturition.

Calcium-Transporting ATPases↗
PubMed1991

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↗
PubMed1994

Studies on the contracture inducing action of triphenyltin in the mouse diaphragm.

Triphenyltin induces a contracture of the mouse phrenic nerve-diaphragm preparation. This contracture was not inhibited by (+)-tubocurarine, high magnesium or the absence of electrical stimulation. Triphenyltin (0.1 mM) reduced the muscle membrane potential, the amplitude of the muscle action potential and the muscle membrane input resistance. Pretreatment with high K+ (25 mM) or veratridine (1.5 microM; a Na+ channel activator) briefly shortened the onset of the contracture and increased the peak tension of the contracture. Pretreatment with tetrodotoxin (0.3 microM; a Na+ channel blocker) or glycerol (a T tubule uncoupler) however, significantly reduced the triphenyltin-induced contracture. Removing Ca2+ from external solution and prolonged treatment with either caffeine (20 mM) or ryanodine (2 microM) inhibited the triphenyltin-induced contracture. However, a brief treatment with a lower concentration of caffeine (10 mM) potentiated the contracture. 45Ca2+ uptake studies showed that triphenyltin caused the muscle to accumulate Ca2+ which entered from external solution. Pretreatment with trypsin and dithiothreitol (a sulfhydryl-containing reducing agent) blocked the contracture induced by triphenyltin. These results suggest that triphenyltin initially interacts with the sulfhydryl groups of membrane bound proteins (possibly the Na+ channel) to cause depolarization of the muscle fibres. This depolarization triggers the release of Ca2+ from sarcoplasmic reticulum through the mechanism of Ca2+ inducing Ca2+ release, activates the contractile filaments and causes the muscle to contract.

Action Potentials↗
PubMed2002

Reproducibility of in vitro contracture test results in patients tested for malignant hyperthermia susceptibility.

BACKGROUND: The in vitro contracture test (IVCT) is the golden standard to diagnose malignant hyperthermia susceptibility (MHS). A high reproducibility is important for a high validity of a test. METHODS: We have therefore analyzed IVCT in 838 patients, investigated in two laboratories. Each halothane and caffeine test was performed in two muscle strips. The test results were analyzed with respect to reproducibility of abnormal outcomes within pairs of tested muscle strips and size of contractures, thresholds and quality criteria. The patients were tested according to the European Malignant Hyperthermia Group protocol (EMHG). To fulfill quality criteria in the EMHG protocol the twitch height should be 10 mN (1 g) or more. For the caffeine test a minimum contracture of 50 mN (5 g) or more at 32 mmol l-1 caffeine could be used as an alternative quality criterion. RESULTS: There was better reproducibility with larger contractures. The correlation between size of contractures and fraction of muscle strips with abnormal contractures was 0.77 or larger. Contractures < 5 mN (0.5 g) were reproducible in less than half of the tests. There was no difference in reproducibility or size of contractures between tests fulfillling all quality criteria and those not fulfillling these criteria. CONCLUSIONS: IVCT responses close to cut off limits, i.e. <5 mN (0.5 g) in the EMHG protocol, are less reproducible and must scientifically be considered as less reliable. The clinical cut off limits must remain unchanged for reasons of clinical safety. The outcome of quality measurements does not influence the test results.

Adult↗
PubMed2004

[Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia].

OBJECTIVE: Theophylline, a methylxanthine, leads to an increase of the cytoplasmic Ca(2+)-concentration in the muscle cell. Since the in-vitro contracture test (IVCT) with halothane and caffeine does not distinguish a 100% between malignant hyperthermia susceptible (MHS) and non-susceptible (MHN), we examined the in-vitro effects of theophylline in porcine skeletal muscle preparations. METHODS: After approval by the local animal care committee ten MHS- and nine MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administrations of theophylline in concentrations of 3.0 respectively 5.0 mmol/l. Muscle contracture development and twitch amplitudes were recorded over a period of 30 minutes. Data are expressed as medians and ranges. RESULTS: After both theophylline bolus administrations MHS-muscles developed significantly higher contractures compared to the MHN-specimens. The MHS-muscles reached a maximum contracture of 17.0 mN (7.2-59.6 mN) after administration of 3.0 mmol/l theophylline. In comparison, two MHN-specimens showed weak contractures with a maximum of 1.4 mN. The 5.0 mmol/l theophylline IVCT resulted in maximum contractures of 19.1 mN (2.1-39.2 mN) for the MHS-preparations. Just in three MHN-muscles weak contractures of 0.0 mN (0.0-0.8 mN) were recorded. Thus, a significant difference without overlap was revealed for the maximum contracture. CONCLUSION: Theophylline in concentrations of 3.0 and 5.0 mmol/l revealed a clear difference between MHS- and MHN-porcine muscle preparations. Further examinations on human skeletal muscles are needed to demonstrate the value of theophylline in the IVCT MH-diagnosis.

Animals↗
PubMed1996

Spasticity and muscle contracture following stroke.

It has become increasingly recognized that the major functional deficits following brain damage are largely due to "negative' features such as weakness and loss of dexterity rather than spasticity. A variety of studies suggest that spasticity is a distinct problem and separate from the loss of dexterity, but that it may be implicated in the formation of muscle contracture and even in the recovery of strength. In order to address these issues, we examined the relationship between spasticity, contracture, strength and dexterity in the affected upper limb following stroke. Spasticity was measured both as increased tonic stretch reflexes and increased resistance to passive stretch (hypertonia). Twenty-four patients were recruited non-selectively from three rehabilitation units within 13 months of their stroke. Few patients exhibited increased tonic reflexes but half were found to have muscle contracture, the earliest at 2 months following stroke. Hypertonia was associated with contracture but not with reflex hyperexcitability. Increased tonic stretch reflexes were observed only in a subgroup of those with contracture and where present could usually be elicited only at the end of muscle range. This findings suggests that instead of spasticity causing contracture, contracture may actually potentiate spasticity in some patients. However, the majority of patients with contracture did not have increased tonic stretch reflexes. In addition, we found no relationship between spasticity and either weakness or loss of dexterity. Therefore, while hypertonia remains an important problem following cerebral lesions, it would appear that the amount of attention directed to reflex hyperexcitability associated with spasticity is out of proportion with its effects. Consequently, hypertonia needs to be clearly distinguished from reflex hyperexcitability in patients with spasticity.

Adult↗
PubMed1993

Halothane and temperature interact to increase succinylcholine-induced jaw contracture in the rat.

BACKGROUND: The agonist actions of succinylcholine (SCh) have recently come under study because of their involvement in the clinical problem of masseter muscle rigidity, and their possible involvement in malignant hyperthermia. The authors investigated factors affecting SCh-induced contractures in an animal preparation. METHODS: Rats were anesthetized with either halothane (1-2%) or pentobarbital. Resting and twitch isometric tension were measured from the jaw muscles. Succinylcholine (500 or 750 micrograms/kg) was administered intravenously, producing increases in resting tension (i.e., contractures). Jaw muscle temperature was controlled by radiant heat. RESULTS: Succinylcholine increased jaw muscle tension for several seconds. These contractures exhibited tachyphylaxis, and were antagonized by vecuronium (0.8-1.5 mg/kg), indicating mediation by acetylcholine receptors (AChR). In the presence of 2% halothane, contractures were tenfold greater at a rectal temperature of 41 degrees C than at 37 degrees C. In contrast, under 50 mg/kg intraperitoneal pentobarbital anesthesia, contractures were not affected by rectal temperature. Neither the half-decay time of contracture nor twitch tension (0.2 Hz, preceding SCh) were increased in the presence of halothane at 41 degrees C. In a set of experiments in which rectal temperature was maintained at 37 degrees C but jaw temperature was varied between 36-41 degrees C, there was a significant regression of SCh-induced jaw contracture on temperature in the presence of halothane. In contrast, there was no significant relationship between jaw temperature and contracture in the presence of pentobarbital. CONCLUSIONS: These results in the rat demonstrate a temperature-dependent interaction between halothane and SCh that has not previously been described.

Animals↗
PubMed1997

Attenuation of serotonin-induced contractures in skeletal muscle from malignant hyperthermia-susceptible patients with dantrolene.

BACKGROUND: Porcine malignant hyperthermia (MH) can be triggered by administration of certain serotonin2 receptor agonists. Pretreatment with dantrolene completely abolished serotonin-induced MH. The purpose of this study was to investigate the effects of the serotonin2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in skeletal muscle specimens from MH-susceptible (MHS) and MH-nonsusceptible (MHN) patients following pretreatment with dantrolene. METHOD: We used muscle specimens surplus to diagnostic requirements from 12 MHS and 13 MHN patients in this study. In the first experiment, DOI 0.02 mM was added to the organ bath. In the second experiment, muscle specimens were preincubated with dantrolene 0.5 microM or 1.0 microM, respectively, for 10 min before DOI 0.02 mM was administered. RESULTS: Administration of DOI 0.02 mM induced contractures in muscle specimens from MHS and MHN patients. Contracture development started significantly earlier in MHS than in MHN specimens. In MHS muscle the maximum contracture was significantly greater than in MHN. Pretreatment with dantrolene significantly delayed the start of contracture development in MHS muscles, whereas in MHN muscles no contractures were observed after dantrolene. The contracture maximum was significantly reduced in MHS. CONCLUSION: The acceleration of DOI-induced contracture development in skeletal muscle specimens from MHS patients indicates that an altered serotonin system might be involved in human MH. Dantrolene effectively delayed serotonin-induced contractures. Further investigations are needed to determine whether serotonin2 receptors of skeletal muscle from MHS subjects are altered in function or structure, or whether this response is a secondary phenomenon.

Adolescent↗
PubMed1979

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↗
PubMed1989

The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine.

1. The protective effects of some calcium antagonists against different forms of calcium overload contracture were investigated in embryonic chick cardiac myocytes. 2. Tetrodotoxin-sensitive sodium currents were recorded from the myocytes by the whole-cell voltage-clamp technique. Although the peak current was attenuated by veratrine, the inactivation process was markedly inhibited, resulting in a large increase in the total inward current. Action potentials were prolonged by veratrine, automaticity was inhibited and the membrane potential depolarized from -79 to around -45 mV. 3. Measurements of contraction were made from aggregates of myocytes using a video edge detection technique which quantified edge movement. Veratrine caused an initial positive inotropism then inhibited automaticity of aggregates with subsequent development of a tonic contracture to around 300% of the twitch contraction. 4. Veratrine-induced contractures were not significantly affected by 10 microM diltiazem or verapamil. Nifedipine (5 microM), nimodipine (5 microM) and ryanodine (5 microM) also had little effect whilst nicardipine and flunarizine caused a concentration-dependent inhibition of veratrine-induced contractures with IC50s of 3 microM and 2 microM respectively. 5. Veratrine-induced contractures were found to be very sensitive to extracellular calcium concentration with an EC50 of 32 microM. Edge movement associated with beating of the myocytes was much less sensitive to calcium (EC50 = 1 mM). Submaximal veratrine contractures in 20-50 microM extracellular calcium were not potentiated by 1 microM Bay K 8644. 6. Tetrodotoxin also inhibited veratrine-induced contractures but did not affect contractions induced by ouabain in the presence of 10 microM diltiazem. 7. Ouabain-induced contractures were also inhibited by nicardipine and flunarizine indicating that these drugs can protect against calcium overload in embryonic chick heart by a mechanism independent of the normal form of voltage-sensitive sodium or calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Prevention by specific chemical classes of alpha 1-adrenoceptor antagonists of veratrine-contractures in rat left atria independently of alpha 1-adrenoceptor blockade.

1. The putative direct protective effects of a series of chemically diverse alpha 1-adrenoceptor antagonists against veratrine alkaloid-induced tetanic contractures in rat isolated left atria have been investigated. 2. Atria were mounted in organ baths containing normal, oxygenated physiological salt solution (20 ml, pH 7.4), for isometric tension recording. Atria were electrically driven at 4 Hz and were maintained at 34 degrees C. Veratrine (100 micrograms ml-1) was applied to the atria to elicit tetanic (diastolic) contracture. 3. Concentration-dependent protective effects against veratrine-contractures, in the absence of negative inotropic responses, were observed with the quinazoline congeners, prazosin and doxazosin and with the benzodioxane-related compounds, WB 4101 and its thio analogue, benoxathian. IC50 concentrations and apparent Hill coefficients of all four drugs ranged from 0.27 to 0.93 microM, and from 0.86 to 1.09, respectively, and are consistent with interaction at a single site. 4. In contrast, no protective activity versus veratrine-contractures was observed with corynanthine, 5-methyl-urapidil, phenoxybenzamine, phentolamine or chloroethylclonidine (10 microM). 5. Contractures were prevented by prazosin at concentrations 2-3 log units higher than those which antagonized methoxamine-evoked inotropic responses. In addition, concomitant alpha 1-adrenoceptor occupancy by high concentrations of methoxamine (100 microM), phentolamine (10 microM, inactive per se in preventing contracture), or both drugs together, failed, in each case, to modify significantly the protective effects of prazosin or WB 4101 against veratrine-contractures. 6. Our findings demonstrate that alpha 1-adrenoceptor antagonists which prevent veratrine-contractures belong to specific chemical classes of the quinazoline- and benzodioxane-type. The mechanism by which these drugs afford protection is apparently independent of an interaction with defined alpha 1-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1981

Slow potassium contractures in mouse limb muscles.

1. Mouse extensor digitorum longus and soleus muscles respond to a sudden maintained increase in external K ion concentration with a fast contracture which inactivates and is followed by a slow contracture. 2. The slow contracture could not be selectively eliminated by altering the tonicity, ionic strength, anionic composition or buffer system of the external solution and depended only on the increase on external potassium concentration. The slow contracture differed from the fast K contracture in its time course, temperature sensitivity, fibre type dependence, and inactivation kinetics. The fast and slow contractures were similarly altered by changes in external anion species, by changes in external divalent cations, and by the presence of 20 mM-caffeine. 3. The mechanism and functional significance of the slow contracture are obscure. The results suggest that its generation is not identical to that of the fast contracture, but may depend, in part, upon the normal activation processes.

Animals↗
PubMed1992

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↗