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The effects of mechanical loading and changes of length on single guinea-pig ventricular myocytes.

1. The effects of mechanical loading and changes of length on the contraction of single guinea-pig ventricular myocytes has been investigated. 2. Cell shortening was monitored during isotonic contractions (in which the cell shortened freely) and after attaching carbon fibres of known compliance to the ends of the cell, so that the cell contracted auxotonically (the cell both shortened and developed force). 3. Mechanically loading the cells decreased the amount of shortening during a contraction and abbreviated the contraction. There were, however, no consistent changes in the action potential or the [Ca2+]i transient (measured with the fluorescent dye fura-2). 4. Increasing stimulation rate increased the size of the contraction and the [Ca2+]i transient in both isotonic and auxotonic conditions. The increase in the size of the contraction induced by an increase in stimulation rate was greater in auxotonic conditions but the increase in the size of the [Ca2+]i transient was not. 5. When cells were stretched, there was a step increase in the size of the contraction and a prolongation of its time course. However, neither the size nor the time course of the accompanying [Ca2+]i transient was significantly altered by this intervention. 6. When a stretch was maintained, a further, slow increase in the size of the contraction occurred during the following 3-11 min, in about half the cells studied. The probability of this slow response occurring was increased if the initial degree of activation of the cell was decreased. 7. These data suggest that the mechanisms underlying the responses to mechanical loading and changes of length are the same in both multicellular and single cell preparations of cardiac muscle.

Animals↗

Substrate dependence and oxygen sensitivity of tone and of spontaneous and evoked contractions of the distal colonic muscularis mucosae of opossum.

The muscularis mucosae of the opossum distal colon fails to maintain tone and to generate spontaneous contractions in an anaerobic environment in vitro. To investigate this phenomenon further, dose-response curves to agonists under different oxygen concentrations were examined. In other experiments the tissue was actively exhausted (i.e., repeatedly stimulated in a substrate-free environment until no response to K+, acetylcholine, or histamine could be observed) and then equilibrated with an alternative substrate for 3 h, when the ability of the tissue to contract to agonists was reevaluated. Reducing the available oxygen abolished tone and caused a graded loss of responses to histamine; in contrast, at 0% oxygen maximum responses to acetylcholine were reduced by only 75%. Abolition of tone by the addition of cyanide to the bathing medium did not affect the amplitude of responses to histamine and acetylcholine. The tissue was able to use all the chosen alternative substrates to different degrees for acetylcholine-induced contraction; similarly, with the exception of beta-hydroxybutyrate it could use all substrates to some degree to support responses to histamine. The evidence suggests that the source of energy required to maintain tone is different from the source required to sustain K+ or agonist-induced contractions, and that the dependence of isotonic contractions on exogenous substrates varies with the pharmacologic stimulus.

Acetylcholine↗

Reactivation of cytoplasmic actomyosin in Physarum plasmodia extracted with glycerol and dimethylsulphoxide.

Thin-spread plasmodia of Physarum were subjected to extraction procedures using 50% glycerol or DMSO (dimethylsulphoxide) followed by labelling of actin with fluorescent phallotoxins. During the reactivation of the actomyosin system by 2 mM-MgATP fluorescent actin fibres contract isotonically, which results in numerous fluorescent 'contraction beads'. After short-term extraction 1 mM-Ca2+ has an inhibitory effect on the reactivation. This calcium sensitivity is abolished after long-term extraction with glycerol. Calcium at 10 mM irreversibly inhibits reactivation, irrespective of the duration of extraction. The inhibitory effect of 10 mM-calcium is prevented by phallotoxin labelling prior to incubation in Ca2+. The DMSO model shows an improvement in structural preservation when compared with the glycerol models. However, reactivation is inhibited by prolonged treatment with DMSO.

Actomyosin↗

Mechanical characterization of a model of a multicomponent cardiac fibre.

We have developed a model of a cardiac fibre composed of several contractile units in series and activated in succession; each unit behaves according to Wong's model. The main difference between the multicomponent model and the classic monocomponent model is that it is possible to take into account both the dynamic phenomena due to the propagation of the activation signal along the fibre and the contractility of each unit from which the fibre is constructed. Isometric and isotonic contractions have been simulated under different conditions in terms of preload, afterload, frequency and number of inhibited units. The analysis of the results allows us to assert that the multicomponent fibre behaviour is in good agreement with experimental results from the literature. We believe that the multicomponent cardiac fibre should be regarded as a powerful tool linking the sarcomere contraction with that of the whole ventricle.

Biomechanical Phenomena↗

Contractions of the filariid Acanthocheilonema viteae induced by potassium chloride.

The effects of K+ on muscle contractility were explored in the filarial nematode Acanthocheilonema viteae (Dipetalonema viteae). The parasite was slit open longitudinally and mounted in a smooth muscle chamber that was filled with aerated (95% N2-5% CO2) physiological solution at 37 degrees C. KCl at concentrations ranging from 20 to 100 mM induced a rapid isotonic contraction of the filarial muscle. The maximal response from KCl was similar to the maximal response to acetylcholine chloride (ACh). When KCl was applied for several minutes, tolerance frequently occurred. Contractions were also induced by K2SO4 but not by NaCl, Na2SO4 or sucrose. Nifedipine was more than 10 times as potent in reducing the KCl-induced contraction as in reducing that caused by ACh. The KCl-induced contraction was abolished in a Ca-free physiological medium containing ethyleneglycol-bis-(beta-aminoethyl ether) N, N, N', N'-tetraacetic acid (EGTA, 10(-4) M). Low [Ca2+]/[Mg2+] solutions blocked the spontaneous activity, the KCl-induced contractions, and the ACh-induced contractions. KCl also induced contractions in denervated muscle strips, supporting the hypothesis that K+ acts directly on the muscle cells. These results indicate that K+ can depolarize the muscle membrane and induce a muscle contraction that is dependent on extracellular calcium ions.

Animals↗

Corticosteroid effects on isotonic contractile properties of rat diaphragm muscle.

The effects of corticosteroids (CS) on diaphragm muscle (Diam) fiber morphology and contractile properties were evaluated in three groups of rats: controls (Ctl), surgical sham and weight-matched controls (Sham), and CS-treated (6 mg . kg-1 . day-1 prednisolone at 2.5 ml/h for 3 wk). In the CS-treated Diam, there was a selective atrophy of type IIx and IIb fibers, compared with a generalized atrophy of all fibers in the Sham group. Maximum isometric force was reduced by 20% in the CS group compared with both Ctl and Sham. Maximum shortening velocity in the CS Diam was slowed by approximately 20% compared with Ctl and Sham. Peak power output of the CS Diam was only 60% of Ctl and 70% of Sham. Endurance to repeated isotonic contractions improved in the CS-treated Diam compared with Ctl. We conclude that the atrophy of type IIx and IIb fibers in the Diam can only partially account for the CS-induced changes in isotonic contractile properties. Other factors such as reduced myofibrillar density or altered cross-bridge cycling kinetics are also likely to contribute to the effects of CS treatment.

Adrenal Cortex Hormones↗

Reversible alterations in excitation-contraction coupling during myocardial hypertrophy in rat papillary muscle.

To investigate the possible role of an alteration in excitation-contraction coupling in cardiac hypertrophy, we compared simultaneously recorded action potentials along with isometric or isotonic contractions of normal and hypertrophied papillary muscles. Hypertrophy was produced by renal hypertension in rats. Hypertrophied papillary muscles were taken from rats that had been hypertensive for 10 [HBP (10)] or 20 [HBP (20)] weeks. Regression of changes induced by hypertrophy was studied in rats that had been hypertensive for 10 weeks and then made normotensive for 10 weeks by removal of the ischemic kidney. Papillary muscles from age-matched, sham-operated rats [SHAM (10), SHAM (20)] were used as controls. We found that HBP (10) rats had significantly longer action potentials than SHAM (10) rats and that difference in the action potential duration recorded during isotonic and isometric contractions was significantly different from SHAM (10) and HBP (10) rats. Peak developed tension was the same in HBP (10) and SHAM (10) muscles, but the duration of isometric contraction and time-to-peak shortening were longer in HBP (10) muscles. Similarly, whereas the peak tension was the same in HBP (20) and SHAM (20) muscles, the duration of the action potential and isometric contraction, as well as the time-to-peak tension, was longer in HBP (20) muscles. The longer values for action potential duration, isometric contraction, and time-to-peak tension in HBP (20) muscles returned to SHAM values in HBP (R) muscles. The functional relationship between contraction and the action potential time course was assessed by plotting action potential duration against four parameters of contraction: peak developed tension, time-to-peak tension, time-to-half relaxation, and time-to-peak shortening. Statistical analysis of these data showed a significant correlation between action potential duration and all four parameters of contraction in SHAM (10) and SHAM (20) muscles. In contrast, HBP (10) muscles showed a significant correlation between action potential duration and only two contractile parameters, whereas action potential duration did not correlate significantly with any of the contractile parameters in HBP (20) muscles. Remarkably, in HBP (R) preparations a significant correlation was restored between action potential duration and three of the four contractile parameters. The results of this study suggest that reversible cardiac hypertrophy is associated with reversible alterations in excitation-contraction coupling. The reversibility of the mechanical and electrical alterations that accompany hypertrophy suggests, in turn, that cardiac hypertrophy is an adaptive process.

Action Potentials↗

A joint model of the contractile system of striated muscle (dynamic version).

The Joint Model of the Contractile System of Muscle is a theoretical construction and the question is whether it may express adequately some aspects of the biological original. In addition to the previous results which presented preliminary calculations, simulation experiments have been performed with a dynamic version of the model. The relations found between the variables studied (length, shortening velocity, isotonic contraction load, shortening heat production rate and excess of effective activity), did not essentially differ from those established by preliminary calculations; the choice of appropriate parameter values and the introduction of some additional features in the system made it possible to obtain a better approximation of relations known from measurements on the biological object. The model discloses some relevant general aspects of the contractile system of "independent" generators of force and thus contributes to a specification of the relationships between molecular and macroscopic levels of contraction phenomena. Future development or correction of the concepts under consideration depend on more suitable empirical data and further simulation experiments.

Biomechanical Phenomena↗

Some electrical and mechanical effects of strontium on toad ventricular muscle: comparison to calcium.

1. The mechanical and electrophysiological effects of Sr were evaluated and compared to those of Ca in isolated, electrically driven toad ventricular muscle strips. The effects of Ca and Sr were compared at concentrations from control (2 mM) to 10 mM either by substitution of Sr for Ca at equimolar concentration, or by maintenance of a constant total Ca plus Sr concentration within which individual Ca and Sr concentrations were varied. 2. Changes in the degree of contractile activation were evaluated in terms of changes in maximal dT/dt of isometric contractions, maximal dL/dt of very lightly loaded isotonic contractions, and the shape of after-loaded force-velocity curves, with specific attention directed to the shape of the curves as they approached Vmax on the velocity axis. Effects on the cell membrane were evaluated in terms of changes in the transmembrane action potential (recorded with glass micro-electrodes) and in the mechanical parameters directly related to its duration in amphibian ventricle, viz. the duration of isometric tension and of isotonic shortening. Isometric tension and action potentials were recorded simultaneously. 3. Ca and Sr, at concentrations above control, had similar but not identical effects on dT/dt and dL/dt. Both ions alone in equimolar concentrations, or together at constant total Ca plus Sr concentration, increased dT/dt and dL/dt and shifted force-velocity curves upward. At constant total Ca plus Sr concentration, force-velocity curves were virtually superimposable as they approached the velocity intercept. 4. The duration of the action potential was markedly prolonged by Sr and shortened by Ca in concentrations above control. Unlike dT/dt and dL/dt, the total duration of isometric tension and isotonic shortening depended upon the specific Ca and Sr concentrations within a constant total concentration, and were progressively prolonged as the Sr concentration was increased. 5. The similar effects of Ca and Sr on dT/dt, dL/dt, and on the force-velocity relationship at light loads depended upon the presence of Ca ions. In Sr alone, dT/dt and dL/dt were faster than in an equimolar concentration of Ca, and time to maximal dT/dt and dL/dt was prolonged. The force-velocity curve in Sr alone was consistently shifted upward beyond the other curves in which Ca was present. These differences between the two ions are attributed in part to the rapid and early repolarization of the action potential in elevated Ca and the resultant abbreviation of the build up in active state and slower dT/dt and dL/dt. 6. The results suggest that Ca and Sr act in a similar although not identical way in activating contraction but are competitive at the cell membrane.

Action Potentials↗

Adaptive cancellation of muscle contraction interference in vibroarthrographic signals.

Vibroarthrography (VAG) is an innovative, objective, non-invasive technique for obtaining diagnostic information concerning the articular cartilage of a joint. Knee VAG signals can be detected using a contact sensor over the skin surface of the knee joint during knee movement such as flexion and/or extension. These measured signals, however, contain significant interference caused by muscle contraction that is required for knee movement. Quality improvement of VAG signals is an important subject, and crucial in computer-aided diagnosis of cartilage pathology. While simple frequency domain high-pass (or band-pass) filtering could be used for minimizing muscle contraction interference (MCI), it could eliminate possible overlapping spectral components of the VAG signals. In this work, an adaptive MCI cancellation technique is presented as an alternative technique for filtering VAG signals. Methods of measuring the VAG and reference signals (MCI) are described, with details on MCI identification, characterization, and step size optimization for the adaptive filter. The performance of the method is evaluated by simulated signals as well as signals obtained from human subjects under isotonic contraction.

Adult↗

Extraneuronal uptake inhibitor U-0521 decreases contractile responses in rat vas deferens.

1. The influence of catechol-O-methyltransferase inhibitor U-0521 on isotonic contraction of isolated rat vas deferens was examined to determine optimal concentration and nonspecific effects. 2. Maximum responses to (-)-epinephrine were increased at 0.4 microM and 1 microM concentrations of U-0521. Epinephrine responses were progressively decreased in the presence of higher concentrations (10 microM, 30 microM and 100 microM) of U-0521. 3. The response to the nonadrenergic agonist neurokinin A was similarly depressed in the presence of 100 microM U-0521. 4. U-0521 not only inhibits COMT, at concentrations above 1 microM it nonspecifically depresses contraction of the rat vas deferens by both adrenergic and nonadrenergic agonists.

Adrenergic alpha-Agonists↗

Relative contributions of ATP and noradrenaline to the nerve evoked contraction of the rabbit jejunal artery. Dependence on stimulation parameters.

Isotonic contractions of the rabbit jejunal artery were evoked by perivascular nerve stimulation with trains of 10 or 100 stimuli at 2 Hz or 10 Hz. Short trains of stimuli elicited contractions that were totally resistant to alpha-adrenoceptor blockade (0.1 mumol/l prazosin) but blocked by alpha,beta-methylene ATP (1 mumol/l). A substantial noradrenergic component of contraction comprising about 50% of the total could be evoked by adjusting the stimulation parameters (increasing the frequency and/or number of stimuli in a train). The noradrenergic and the purinergic components are derived from sympathetic nerves as both were blocked by TTX and the adrenergic neurone blocker guanethidine (3 mumol/l). It is concluded that the contraction of the rabbit jejunal artery to short trains of stimuli is predominantly purinergic, a noradrenergic component only being revealed at higher frequencies of stimulation or during longer trains of stimuli. The purinergic component of contraction is derived from sympathetic nerves and not from a separate population of purinergic nerves.

Adenosine Triphosphate↗

The inhibition of muscle contraction by adenosine 5' (beta, gamma-imido) triphosphate and by pyrophosphate.

We have studied the inhibition of the contraction of glycerinated rabbit psoas muscle caused by ligands that bind to the ATPase site of myosin. Two ligands, adenosine 5' (beta, gamma-imido) triphosphate (AMPPNP) and pyrophosphate (PPi), decreased the force and stiffness developed in isometric contractions and the velocity of shortening of isotonic contractions. The force exerted by isometric fibers was measured as a function of MgATP in the presence and absence of a constant concentration of the ligands. As the MgATP concentration decreased, the inhibition of tension caused by the ligand increased, reaching approximately 50% at 25 microM MgATP and either 2 mM MgPPi or 2 mM MgAMPPNP. The maximum velocity of shortening was also measured as a function of MgATP concentration in the presence of 1 and 2 mM MgPPi and 2.5 and 5 mM MgAMPPNP. Both ligands acted as pure competitive inhibitors with Ki = 3.0 mM for PPi and 5.1 mM for MgAMPPNP. These data show that both ligands are weak inhibitors of the contraction of fibers. The results provided information on the energetics of actin-myosin-ligand states that occur in the portion of the cross-bridge cycle where MgATP binds to myosin. A simple analysis of the inhibition of velocity suggests that MgAMPPNP binds to the actomyosin complex at this step of the cycle with an effective affinity constant of approximately 2 X 10(2) M-1.

Adenosine Triphosphate↗

Function dependent changes in the subcellular distribution of high energy phosphates in fast and slow rat skeletal muscles.

Function dependent changes in the subcellular distribution of ATP, ADP, creatine phosphate (CrP) and creatine (Cr) in rat fast-twitch gastrocnemius and slow-twitch soleus muscles were studied by fractionation of freeze-clamped and freeze-dried tissue in non-aqueous solvents. During 5 min of isotonic contraction of gastrocnemius muscles the mitochondrial content of total creatine [sigma(CrP + Cr)] decreases by 9.5 nmol/mg total protein whereas there is an increase in extramitochondrial total creatine by 12.3 nmol/mg total protein, indicating a net transfer of approximately 10 nmol total creatine/mg total protein/5 min across the mitochondrial inner membrane. During short-term stimulation (6 s) of gastrocnemius muscles the socalled "additionally-bound ADP" correlates not only with force (Hebisch et al. 1984) but also with filament overlap. This confirms the previous suggestion that "additionally-bound ADP" represents actomyosin-ADP-complexes. Following long-term stimulation (10 s), the rate of decay of force is at least two orders of magnitude faster than that of "additionally bound ADP". This indicates a decrease of actomyosin-ADP complexes due to formation of myosin-ADP complexes. Short-term stimulation (6 s) of slow-twitch soleus muscles does not lead to any force-dependent change in the content of "additionally-bound ADP", similar to the finding in long-term contracting gastrocnemius muscles. Denervation of soleus muscles leads to a decrease in "additionally-bound ADP" to values comparable to those found in resting fast-twitch gastrocnemius muscles.

Adenosine Diphosphate↗

An equilibrium-point model for fast, single-joint movement: II. Similarity of single-joint isometric and isotonic descending commands.

The model for isotonic movements introduced in the preceding article in this issue is used to account for isometric contractions. Isotonic movements and isometric contractions are analyzed as consequences of one motor program acting under different peripheral conditions. Differences in isotonic and isometric EMG patterns are analyzed theoretically. Computer simulation of the EMG patterns was performed both with and without the inclusion of possible effects of reciprocal inhibition. A series of experiments was performed to test the model. The subjects made fast isotonic movements that were unexpectedly blocked at the very beginning in some of the trials. The observed differences in the EMG patterns between blocked and unblocked trials corresponded to the model's predictions. The results suggest that these differences are due to the action of a tonic stretch reflex rather than to preprogrammed reactions. The experimental and simulation findings, and also the data from the literature, are discussed in the framework of the model and the dual-strategy hypothesis. They support the hypothesis that the motor control system uses one of a few standardized subprograms, specifying a small number of parameters to match a specific task.

Journal Article↗

Fatigue and recovery of power and isometric torque following isotonic knee extensions.

The purpose of this study was to assess fatigue and recovery of isotonic power and isometric contractile properties after a series of maximal isotonic contractions. Using a Biodex dynamometer, 13 men [26 yr (SD 3)] performed isotonic [50% of isometric maximal voluntary contraction (MVC) every 1.2 s through 75 degrees range of motion] single-limb knee extensions at the fastest velocity they could achieve until velocity was reduced by 35%. Time to task failure was 38 s, and, compared with baseline, power declined by approximately 42% [741.0 (SD 106.0) vs. 426.5 W (SD 60.3) at task failure], and MVC declined by approximately 26% [267.3 (SD 42.5) vs. 198.4 N.m (SD 45.7) at task failure]. Power recovered by 5 min, whereas MVC did not recover, and at 10 min was only approximately 85% of baseline. Isometric MVC motor unit activation was approximately 95% at rest and was unchanged at task failure (approximately 96%), but a small amount of failure was apparent between 1.5 and 10 min of recovery (approximately 87 to approximately 91%). Half relaxation time measured from a 50-Hz isometric tetanus was significantly prolonged by approximately 33% immediately after task failure but recovered by 1.5 min. A decline in the 10- to 50-Hz ratio of the evoked isometric contractions was observed at 5 and 10 min of recovery, which suggests excitation-contraction coupling impairment. Changes in velocity and half relaxation time during the protocol were strongly and negatively correlated (r = -0.85). Thus mainly peripheral mechanisms were implicated in the substantial depression but relatively fast recovery of isotonic power. Furthermore, isometric muscle contractile properties were related to some, but not all, changes in isotonic function.

Adult↗

Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum.

Ginger (rhizomes of Zingiber officinale) has been shown to exert potent anti-emetic properties, but its mode of action has not yet been elucidated. Among its active constituents, [6]-, [8]- and [10]-gingerol as well as [6]-shogaol were shown in different in vivo studies to be at least partly responsible for the drug's anti-emetic properties. In an attempt to gain more insight into the mode of action of these compounds, three different in vitro models were used to investigate their effects on 5-HT(3) receptors (serotonin receptor subtype) in more detail: [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated guinea-pig ileum and equilibrium competition binding studies using a radioactively labeled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). All four compounds inhibited the [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the guinea-pig ileum induced by SR57227A ((4-amino)-(6-chloro-2-pyridyl)l-piperidine hydrochloride), a highly selective 5-HT(3) receptor agonist. Both effects were concentration-dependent, with the following order of potency for both models: [6]-shogaol> or =[8]-gingerol>[10]-gingerol> or =[6]-gingerol. All compounds showed also weak anticholinergic and antineurokininergic activities in the guinea-pig ileum (acetylcholine and substance P are mediators of the 5-HT(3) receptor effect). The vanilloid receptor did not seem to be involved derived from experiments using capsazepine. None of the tested ginger substances, however, was able to displace [(3)H]GR65630 from its binding site (5-HT(3) receptor) neither on intact N1E-115 cells nor on the purified membranes of HEK-293 cells over-expressing the h5-HT(3) receptor. It may be concluded that [6]-, [8]-, [10]-gingerol and [6]-shogaol exert their anti-emetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site. This may include indirect effects via receptors in the signal cascade behind the 5-HT(3) receptor channel complex such as substance P receptors and muscarinic receptors; this needs further investigation since ginger is effective against motion sickness which is cured by some vanilloids and by anticholinergics such as scopolamine.

Animals↗

Electromyographic analysis of the sternohyoid muscle and anterior belly of the digastric muscle in jaw movements.

The sternohyoid muscle and the anterior belly of the left digastric muscle were studied electromyographically in 20 young adult volunteer individuals. A surface monopolar electrode and a needle monopolar electrode, inserted into the muscle mass 1.0 cm apart were employed. The most significant action of the two muscles was found in the opening of the jaw, during which the sternohyoid muscle presented an isotonic contraction, allowing for displacements of the hyoid bone. They also acted on those movements that included one of the jaw depression components, such as protrusion, lateral movements to either side, and retrusion. They were inactive when the jaw was in the resting position. Both muscles operated simultaneously most of the time, but a synchronization of their actions could not be demonstrated.

Action Potentials↗