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At least 19 recordsLinked to original sources
PubMed1978

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↗
PubMed1975

Acid-base changes and excitation-contraction coupling in rabbit myocardium. I. Effects on isometric tension development at different contraction frequencies.

The effects of changes in acid-base parameters on the active force of isolated rabbit papillary muscles were studied at contraction frequencies of 12, 60 and 120/min. When extracellular pH was lowered from 7.4 to 7.0 and 6.7 in a bathing solution buffered with 10 mM histidine, the active force decreased at all contraction frequencies studied. After parallel increases of HCO3-minus concentration (up to 47 mM) and PCO2 at a constant extracellular pH of 7.4 the active force of the muscle increased at low and decreased at high contraction frequencies. None of these effects can be attributed to catecholamine release or to altered extracellular concentration of ionized calcium. The inotropic effects produced by bicarbonate were not reproducible by methyl sulfate (47 mM) or propionate (47 mM). It is concluded that: 1. a lowering of the extracellular pH has a negative inotropic effect at all frequencies, 2. HCO3-minus has a positive inotropic effect that is most pronounced at low contraction frequencies and 3. CO2 has a negative inotropic effect exceeding that produced by the mere reduction in extracellular pH. The cellular mechanisms involved in the various inotropic effects are discussed.

Animals↗
PubMed1978

[Effect of neural regulation on the fluctuations in the intervals between cardiac contractions and the force of the contractions].

Statistical analysis of the cardiac rhythm according to the R--R intervals and the force of contractions according to their amplitude was undertaken. The variation coefficient (N%) reflecting the degree of irregularity of intervals between the contractions and the force of contractions during maximum cardiac hyperfunction induced by clamping the aorta for 30 sec was determined. Vagotomy led to a decrease in the irregularity for cardiac rhythm and force of cardiac contractions.

Animals↗
PubMed1979

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↗
PubMed1975

Ultrastructure of the contractile system of striated skeletal muscle and the processes of muscular contraction. II. Releasing system and mechanisms of muscular contraction.

The tropomyosin-troponin system of the thin filaments acts as a regulator of the interaction of myosin with actin by a process of inhibition. This inhibition is released by Ca2+ ions. Muscle contraction occurs when Ca+2 ions are released from the sarcoplasmic reticulum into the myofibril, where they interact with the troponin of the thin filaments. Muscular contraction is due to the sliding of the two kinds of filaments past each other in the hexagonal network of the myofibril. Many hypotheses have been formulated concerning the intimate molecular mechanisms responsible for the sliding of the filaments past each other, but none of these can be considered to be entirely satisfactory.

Actins↗
PubMed1976

The response of fast and slow nuclear bag fibres and nuclear chain fibres in isolated cat muscle spindles to fusimotor stimulation, and the effect of intrafusal contraction on the sensory endings.

1. The mechanical behaviour of intrafusal muscle fibres during fusimotor stimulation and passive stretch was observed directly in muscle spindles isolated from the cat tenuissimus muscle. 2. Mammalian intrafusal muscle fibres are of three functional types. Most spindles contain one slow nuclear bag fibre, one fast nuclear bag fibre, and four or five nuclear chain fibres. 3. Contraction in slow nuclear bag fibres is characterized by a long latency and very slow initial velocity, whereas the latency for the other intrafusal fibres is short and the inital velocity rapid. The mean time for maximum contraction (at 75 Hz to 100 Hz) and relaxation is significantly longer for slow nuclear bag fibres (0-8s) than for other intrafusal fibres (0-5 s). The contraction time of fast nuclear bag fibres is sometimes longer than that of nuclear chain fibres but the mean values are not significantly different; a difference in the time to attain 90% contraction is more obvious. 4. At low stimulation frequencies (10 Hz) contraction in slow nuclear bag fibres and in most fast nuclear bag fibres is smooth whereas nuclear chain fibres exhibit marked oscillations. Single stimuli elicit small local twitches in nuclear chain fibres and occasionally in fast nuclear bag fibres but produce no visible effect in slow nuclear bag fibres. 5. Maximum contraction of slow and fast nuclear bag fibres at body temperature is attained at a stimulation frequency of 75 Hz to 100 Hz, whereas a frequency of 150 Hz or more is required for maximum contraction of nuclear chain fibres. At 50 Hz at body temperature contraction in nuclear bag fibres is at least half the maximum, whereas in many spindles nuclear chain fibres show only a very small contraction at this frequency. 6. Contraction in slow nuclear bag fibres occurs at one or two discrete foci, most of which lie in the intracapsular region beyond the end of the fluid space. Weak contraction extends the primary sensory spiral by a small amount (2%-8%) at a low velocity (5%-10%s-1). When the fibre is passively stretched the spiral opens and then creeps back to about 75% of the extension at the end of the stretch due to yielding in the poles of fibre; creep is complete in 0-5s to 2-5s. 7. Contraction in fast nuclear bag fibres also occurs at one or two discrete foci, most of which lie in the intracapsular region beyond the end of the fluid space. Shortening of sarcomeres at the foci and extension of the sensory spiral are, however, up to eight times greater (up to 25%) than in slow nuclear bag fibres, and the velocity of stretch of the spiral is three to eight times greater (25%-40%s-1). Fast nuclear bag fibres exhibit little or no creep following passive stretch. 8. Contraction in the nuclear chain fibre bundle is localized to the intracapsular region, centered on a point in the intracapsular region between 0-9 mm and 1-6 mm from the spindle equator. Maximal contraction stretches primary and secondary sensory endings by 15% to 20%, at 30% to 40% s-1...

Animals↗
PubMed1977

[Left ventricular contraction reserve in coronary heart disease. Evaluation, quantification and prognostic value (author's transl)].

Regional and overall left ventricular contraction reserve was studied in 14 patients with coronary heart disease, in 5 healthy subjects and in 4 patients before and after aorto-coronary bypass surgery. Quantification of overall contraction was based on ventricular volumes and ejection fraction. Regional contraction reserve was calculated with the hemiaxis method and a ventricular score. Contraction reserve under nitroglycerin and in postextrasystolic beats was compared. For routine quantification of contraction reserve the ventricular score is recommended. For research purposes the hemiaxis method is to be preferred. Postextrasystolic beats are better suited for analysis of contraction reserve than are angiograms following administration of nitroglycerin. This is due to the minor expense of the procedure, furthermore, postextrasystolic beats allow better differentiation between contracting and non-contracting areas. Left ventricular contraction reserve is larger in patients with coronary heart disease, angina pectoris and ischemic reactions in the exercise ECG than in control patients. These findings are based on overall and on regional volume parameters. A quantitatively greater improvement in contraction could be provoked in the anterior wall than in the posterior wall. Regional contraction improved significantly in most cases either in the anterior wall or in the posterior wall; rarely it improved simultaneously in both left ventricular regions. In a few cases contraction deteriorated in one area with a simultaneous improvement in the opposite area. Overall and regional ventricular function, as assessed preoperatively by contraction reserve determinations could not be completely regained in normal beats after successful bypass surgery. Differences in the regional contraction reserve seemed to be mainly due to varying degrees of ischemia and scarring.

Angina Pectoris↗
PubMed1977

Measurements of contraction latencies to mechanical and electrical stimulation of the protozoan, Spirostomum ambiguum.

Measurements made on contraction latencies in Spirostomun suggest that mechanical stimulation causes contractions to be initiated by the release of small amounts of calcium from a store tightly coupled to the contractile apparatus. Contraction to electrical stimulation appears to result from the gross electrophoretic mobilization of large amounts of calcium from a loosely coupled store. Contraction latencies to mechanical stimulation were three milliseconds and were independent of stimulus strength, previous stimulation, and contraction probability. For 0.5-millisecond biphasic electrical stimulation the contraction latencies varied widely. Latencies to initial contractions were dependent on stimulus strength: from 1.0 milliseconds for a stimulus that caused a 100% probability of contraction to 2.0 milliseconds for a stimulus that caused a 10% probability of contraction. Latencies of contraction to electrical stimulation were also dependent upon previous stimulation, lengthening to over 300 milliseconds after ten minutes of stimulation. Initial contraction latencies were not affected by previous stimulation to the other (electrical or mechanical) stimulus modality. Repeated electrical stimulation also reduced the animal's resting length and slowed the rate of post contraction re-extension, whereas mechanical stimulation did not have these effects.

Animals↗
PubMed1977

The contractile basis of amoeboid movement. V. The control of gelation, solation, and contraction in extracts from Dictyostelium discoideum.

Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature.

Actins↗
PubMed1978

Recruitment order of human spindle endings in isometric voluntary contractions.

1. The responses of twenty-two spindle endings in the anterior tibial and toe extensor muscles of human subjects were studied during isometric voluntary contractions of the receptor-bearing muscle with the ankle joint fixed in 25 degrees plantar flexion.2. The discharge of eighteen endings accelerated in voluntary contractions when the contraction strength exceeded a threshold level which differed for different endings but was reproducible for the same ending.3. With contractions of slow onset the latency to spindle acceleration varied with the speed of onset of the contraction. Endings with a background discharge were often unloaded by contractions until the contraction strength exceeded the threshold for activation of the ending.4. No correlation was found between the sensitivity of a spindle to external length changes and its ease of activation in a voluntary contraction. For two spindle endings with a background discharge there was no change in either discharge frequency or the regularity of spindle discharge during contractions which were below the threshold for activation of the endings. It is concluded that the threshold for activation of a spindle ending in an isometric voluntary contraction is determined by its fusimotor innervation, and that fusimotor neurones probably have a recruitment order, much as do skeletomotor neurones.5. Once activated, the discharge of spindle endings fluctuated with changes in skeletomotor activity but the relationship for some endings contained non-linearities. Such non-linearities were not as apparent in multi-unit recordings from a number of spindle endings in the contracting muscle. It is concluded that the fusimotor drive to a muscle is proportional to the skeletomotor drive to the muscle, and that skeletomotor and fusimotor neurones are subjected to similar if not identical descending command signals. From the work of Evarts (1968), it seems likely that these command signals are related more to desired muscle force than to desired muscle length.

Action Potentials↗
PubMed1979

The contractile basis of ameboid movement. VI. The solation-contraction coupling hypothesis.

The contracted pellets derived from a high-speed supernate of Dictyostelium discoideum (S3) were investigated to determine the functional activity associated with this specific subset of the cellular motile apparatus. A partially purified model system of gelation and contraction (S6) was prepared from the contracted pellets, and the presence of calcium- and pH-sensitive gelation and contraction in this model demonstrated that a functional cytoskeletal-contratile complex remained at least partially associated with the actin and myosin during contraction. Semi-quantitative assays of gelation and solation in the myosin-free preparation S6 included measurements of turbidity, relative viscosity, and strain birefringence. The extent of gelation was optimal at pH 6.8 and a free calcium ion concentration of approximately 3.0 x 10(-8) M. Solation was favored when the free calcium ion concentration was greater than 7.6 x 10(-7) M or when the pH was increased or decreased from pH 6.8. Gelation was reversibly inhibited by increasing the free calcium ion concentration to approxomately 4.6 x 10(-6) M at pH 6.8. The solation-gelation process of this model has been interpreted to involve the reversible cross-linking of actin filaments. The addition of purified D. discoideum myosin to S6 served to reconstitute calcium- and pH-regulated contraction. The results from this study indicate that contraction is coupled functionally to the local breakdown (solation) of the gel. Therefore, solation has been identified as a structural requirement for extensive shortening during contraction. We have called this concept the solation-contraction coupling hypothesis. Fractionation of a preparation derived from the contracted pellets yielded a fraction consisting of actin and a 95,000-dalton polypeptide that exhibited calcium-sensitive gelation at 28 degrees C and a fraction composed of actin and 30,000- and 18,000-dalton polypeptides that demonstrated calcium-sensitive genlation at 0 degrees C.

Calcium↗
PubMedDate not supplied

The contraction induced by ethylenediaminetetracetic acid-4 sodium (EDTA-4Na) in guinea-pig isolated vas deferens kept in isotonic sucrose medium.

1. Ethylenediaminetetracetic acid--4 sodium (EDTA--4Na) induced a contraction in guinea-pig isolated vas deferens kept in isotonic sucrose medium containing 0.07% Nahco3 and 0.1% glucose after preincubation in Locke's solution. The maximum contraction was 82.1 +/- 6.7% of that induced by added KCl. 2. EDTA--Ca--2Na (10(-7) to 10(-3) g/ml) induced no contraction in preparations kept in the sucrose medium. 3. The EDTA--4Na-induced contraction was also obtained when sucrose in the sucrose medium was replaced by glucose but not when the preparation was kept in Locke's solution. 4. The EDTA--4Na-induced contraction was decreased by reduction of the CaCl2 of KCl concentration of the Locke's solution in which the preparation had been preincubated before placing in the sucrose medium. 5. The EDTA--4Na-induced contraction was suppressed with increasing concentrations of NaCl used to partially replace sucrose in the sucrose medium. 6. When the preparation was kept in EDTA-free sucrose medium after pretreatment with 10(-4) g/ml of EDTA--4Na in the sucrose medium for 20 min, a contraction was induced by added CaCl2. The maximum contraction induced by CaCl2 was 30.1 +/- 11.8% of that of the EDTA--4Na-induced contraction, when CaCl2 was added at 20 min after the exchange of medium.

Animals↗
PubMed1977

Excitation-contraction coupling in multiunit tracheal smooth muscle during metabolic depletion: induction of rhythmicity.

Multiunit canine tracheal smooth muscle responded to carbachol with graded depolarization and tonic contraction. The same concentration of carbachol, after metabolic depletion by substrate removal, produced rhythmic contractions and action potentials. Similar mechanical effects were also observed with acetylcholine or histamine. These effects were reversed by reintroducing glucose or beta-hydroxybutyrate, but not by 3-O-methylglucose, which is not metabolized; hence, the structural requirements for glucose, per se, or any osmotic effect were ruled out. Sensitivity to extracellular Ca2+ was increased. A Ca2+-influx blocker, D-600, in low concentration (2 X 10(-8) M) abolished the rhythmic contractions without affecting the tonic contraction. Progressive metabolic depletion in presence of carbachol led to fluctuations in membrane potential with a crest of depolarization and appearance of action potentials, each of which resulted in a small contraction. Many of the small contractions partially fused to form the major rhythmic contractions which appeared at a frequency of one per minute. Rhythmicity could not be produced by increasing extracellular K+ concentration (20-120 mM) in presence of atropine (13(-7) M), but instead a tonic contraction occurred. These results suggest changes in excitation-contraction coupling mechanism with agonists like acetylcholine, carbachol, or histamine during substrate deprivation.

Acetylcholine↗
PubMed1976

[Action mechanism of dibenamine on the tonus and inhibition of drug-induced contraction of the isolated guinea pig ileum, with special reference to its relationship to Ca].

Dibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction(PC) and tonic contraction(TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine-induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentration-action curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site.

Acetylcholine↗
PubMed1976

The responses of human muscle spindle endings to vibration during isometric contraction.

1. An human subjects, vibration of amplitude 1-5 mm and frequency 20-220 Hz was applied to the tendons of muscles in the leg to examine the effects on the discharge of primary and secondary endings during manoeuvres designed to alter the level of fusimotor drive. 2. In four experiments, the peroneal nerve was completely blocked with lidocaine proximal to the recording site in order to de-efferent spindle endings temporarily. The responses to muscle stretch and vibration, as seen in multi-unit recordings and in single unit recordings, were similar during the block as in the relaxed state prior to the block. Thus, these experiments provided no evidence for a functionally effective resting fusimotor drive. 3. The responses to vibration of nine primary endings and four secondary endings were examined during isometric voluntary contractions of the receptor-bearing muscles. Providing that the endings were responding submaximally in the relaxed state, voluntary contraction enhanced the response to vibration, suggesting co-activation of the fusimotor system sufficient to compensate for mechanical unloading. Unloading effects were observed during contractions of neighbouring synergistic muscles, indicating a close spatial relationship between the co-activated skeletomotor and fusimotor outflows. 4. Recordings were obtained from ten primary endings and seven secondary endings during isometric reflex contractions resulting from the vibratory stimulus (TVR contractions). For twelve endings, the appearance of the tonic vibration reflex in the receptor-bearing muscle resulted in a significant decrease in the response to vibration, suggesting that the endings were unloaded by the extrafusal contraction. On voluntary suppression of the reflex contraction spindle responses reverted to their previous levels. 5. These results suggest that the tonic vibration reflex, like the tendon jerk reflex, operates predominantly or exclusively on alpha motoneurones and that it does not utilize the same cortically originating efferent pathways as are used in the performance of voluntary contractions.

Action Potentials↗