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At least 55 records · Page 3Linked to original sources
PubMed2006

Effect of contraction form and contraction velocity on the differences between resultant and measured ankle joint moments.

During a maximal isometric plantar flexion effort the moment measured at the dynamometer differs from the resultant ankle joint moment. The present study investigated the effects of contraction form and contraction velocity during isokinetic plantar/dorsal flexion efforts on the differences between resultant and measured moments due to the misalignment between ankle and dynamometer axes. Eleven male subjects (age: 31+/-6 years, mass: 80.6+/-9.6 kg, height: 178.4+/-7.4 cm) participated in this study. All subjects performed isometric-shortening-stretch-isometric contractions induced by electrical stimulation at three different angular velocities (25 degrees /s, 50 degrees /s and 100 degrees /s) on a customised dynamometer. The kinematics of the leg were recorded using the vicon 624 system with eight cameras operating at 250 Hz. The resultant moments at the ankle joint were calculated through inverse dynamics. The relative differences between resultant and measured ankle joint moments due to axis misalignment were fairly similar in all phases of the isometric-shortening-stretch-isometric contraction (in average 5-9% of the measured moment). Furthermore these findings were independent of the contraction velocity. During dynamic plantar/dorsal flexion contractions the differences between measured and resultant joint moment are high enough to influence conclusions regarding the mechanical response of ankle extensor muscles. However the relative differences were not increased during dynamic contractions as compared to isometric contractions.

Adult↗
PubMed2005

Inhibition of in vitro contractions of human myometrium by mibefradil, a T-type calcium channel blocker: support for a model using excitation-contraction coupling, and autocrine and paracrine signaling mechanisms.

OBJECTIVE: To investigate the importance of T-type calcium channels in human myometrial contractility and to refine a model of contractility. METHODS: We performed in vitro muscle bath experiments on human myometrial tissue strips while simultaneously monitoring bioelectrical activity with loose-contact electrodes. Tissue was obtained by myometrial biopsy from term pregnant women at the time of cesarean delivery and studied after 1 to 7 days in organ culture. Tissue strips were exposed to 5 nM oxytocin to obtain regular contractions. Tissue was then exposed to the T-type calcium channel blocker mibefradil (1 microM), the L-type calcium channel blocker nifedipine (5 nM), or the cyclooxygenase (COX) inhibitor indomethacin (30 microM). All study drugs reduced the strength of contractions. Data were analyzed using a model composed of two phases of force production--an electrical phase (E), which encompassed the first 3 seconds of each contraction, and a paracrine phase (P), which continued until the peak of the contraction. For each phase, the relative force reduction was calculated by the ratio of forces measured after and before drug exposure (RE and RP, respectively). For each drug, experiments were performed in at least triplicate. RESULTS: Myometrial contractions and bioelectrical signals were routinely observed following oxytocin exposure. Spike-like bioelectrical signals occurred only at the beginning of each contraction. Nifedipine and indomethacin slightly modulated the bioelectrical signals, but mibefradil appeared to block the spike component. Mibefradil caused a similar reduction of E and P (RE = 58 +/- 10%, RP = 62 +/- 22%). Nifedipine also reduced E and P, although P was reduced more than E (RE = 72 +/- 12%, RP = 38 +/- 8%, P = .006). Indomethacin yielded variable results, with some experiments showing similar RE and RP values, while other experiments showed RP > RE. CONCLUSION: Mibefradil inhibition of the bioelectrical signal and uterine contractile forces suggest that T-type calcium channels are important in the initiation of each contraction. Some results using indomethacin suggest that for a specific tissue or under some conditions, autocrine stimulation by prostaglandins may be important for recruitment of myocytes in the electrical phase. Stimulation by prostaglandins is likely important in the paracrine phase. Enhanced inhibition by nifedipine in the paracrine phase suggests the mechanism of action of nifedipine tocolytic effect is block of prostaglandin F2alpha (PGF2alpha) paracrine stimulation. Our initial model proposed at least two mechanisms (electrical and nonelectrical) for the recruitment of myocytes. Our modified model suggests that the electrical phase contains a prostaglandin autocrine mechanism in addition to excitation-contraction coupling, and the mechanism in the nonelectrical phase is prostaglandin paracrine signaling.

Adult↗
PubMed1990

Flash photolysis studies of excitation-contraction coupling, regulation, and contraction in smooth muscle.

1. Flash photolysis of caged compounds of phenylephrine, inositol 1, 4, 5 trisphosphate (InsP3), GTP gamma S, ATP, and CTP has been successfully used to study excitation-contraction coupling, contractile regulation, and contraction in smooth muscle. Major processes explored with this method were (a) the delay between agonist-receptor interaction and contraction and between the rise in InsP3, Ca2+ release and contraction; (b) the effect of myosin light chain phosphorylation on the rate of force development and the respective contributions of phosphorylation and crossbridge kinetics to differences between phasic and tonic smooth muscles; (c) the kinetics of the crossbridge cycle. We have also reviewed recent results obtained by other methods and bearing on the mechanisms of pharmacomechanical Ca2+ release and modulation of the Ca2+ sensitivity of the regulatory/contractile apparatus. 2. The long delay (1.5 at 22 degrees C) following activation of alpha 1-adrenergic receptors through photolysis of caged phenylephrine and the high Q10 of this process are consistent with the hypothesis that activation of phospholipase C is the major mechanism of alpha-adrenergic pharmacomechanical Ca2+ release. 3. The delay between photolysis of caged InsP3 and Ca2+ release is short: 30 ms or less, while the latency of contraction is significant (0.3-0.5 s at 22 degrees C) and similar to the lag between the rise in [Ca2+]i and force development in intact smooth muscles. The latency of contraction following photolysis of caged ATP in permeabilized muscles in rigor, in the presence of Ca2+ and calmodulin, is similar, about 0.2-0.5 s at 22 degrees C. 4. In muscles in which the myosin light chains are maintained in a phosphorylated state during rigor, photolysis of caged ATP initiates contractions with a short delay (10 ms or less). This result and those summarized above (2 and 3) suggest that the major portion of the delay between agonist-receptor interaction and contraction is due to activation of phospholipase C and InsP3 production, and about 0.2-0.5 s of the delay (22 degrees C) can be ascribed to prephosphorylation reactions between Ca2+, calmodulin, and myosin light chain kinase, and/or to mechanical processes, or to the chemical kinetics of two-step reactions. 5. Force development from rigor, initiated by photolysis of caged ATP in the presence of Ca2(+)-calmodulin, is rate-limited by myosin light chain phosphorylation; it is significantly accelerated if the myosin light chains are already phosphorylated prior to photolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

[Mechanism of inhibitory effects of ethanol on gallbladder contraction: differences in cases of histamine- and acetylcholine-induced contraction].

We investigated the effects of different concentrations of ethanol on contraction of gallbladder isolated from guinea pig. Ethanol at 25 mM significantly inhibited the contraction induced by histamine, but not those by KCl and acetylcholine. A higher concentration (100 mM) of ethanol inhibited both histamine-, acetylcholine- and KCl- induced contractions. The inhibitory effect of the lower concentration (25 mM) of ethanol was not observed in the presence of verapamil, an antagonist of L-type Ca2+ channel or staurosporine, a selective inhibitor of protein kinase C. Verapamil and staurosporine significantly inhibited both histamine- and acetylcholine-induced contractile responses: the inhibitory effect was more potent for the histamine contraction. Our recent study has demonstrated that contraction caused by protein kinase C activation is completely dependent on Ca2+ influx through the L-type Ca2+ channel in gallbladder smooth muscle of guinea pig. Therefore, the difference in 25 mM ethanol effect on histamine- and acetylcholine-induced contractions may be due to different degree of involvement of protein kinase C activation in the agonist-induced contraction. On the other hands, the higher concentration (100 mM) of ethanol inhibits the common pathway of contraction in gallbladder smooth muscle cells.

Acetylcholine↗
PubMed1992

Effects of propiverine hydrochloride on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog.

The effects of propiverine hydrochloride (P-4, CAS 60569-19-9), a new drug to treat pollakiuria, was investigated on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog. At 10(-6)-10(-5) mol/l P-4 raised the base line of an isolated guinea-pig urinary bladder strip and accelerated its spontaneous contraction. At 10(-4) mol/l P-4 raised, and then lowered the baseline, and accelerated then suppressed its spontaneous contractions. Papaverine at 10(-6)-10(-4) mol/l also showed a similar action as P-4 in the isolated guinea-pig urinary bladder strip. Flavoxate at 10(-6)-10(-4) mol/l raised its base line and accelerated its spontaneous contractions. Those of P-4 at 10(-5) mol/l were not inhibited by tetrodotoxin 10(-6) mol/l). At doses of 50 mg/kg or more, intraduodenal administration of P-4 suppressed the frequency of rhythmic urinary bladder contractions of anesthetized dog in a dose-dependent manner. These results indicate that P-4 shows mainly an accelerating action on the endogenous spontaneous contractions of urinary bladder, but on exogenous contractions induced by the Balloon's method it shows an suppressing action and regulates the functions of the urinary bladder, so P-4 might become a useful drug for the clinical treatment of micturitional dysfunction, for example, pollakiuria.

Anesthesia↗
PubMed1994

Prostaglandin H2 as an endothelium-derived contracting factor modulates endothelin-1-induced contraction.

OBJECTIVE: To investigate the possible involvement of prostaglandin H2, an endothelium-derived contracting factor in the rat aorta, in the development of the contraction induced by endothelin-1. METHODS: The aortic rings from spontaneously hypertensive rats (SHR) were prepared, and the changes of isometric tension of these rings developed by endothelin-1 were recorded with or without the treatment of several inhibitors or an antagonist. The concentrations of prostaglandins and thromboxane B2 in the bath solution with the rings contracted by endothelin-1 were measured by radioimmunoassay. The effects of a thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) on endothelin-1-induced contraction were compared in SHR and Wistar-Kyoto (WKY) rats. RESULTS: Indomethacin (10(-5) mol/l) and ONO-3708 (10(-6) mol/l) significantly diminished endothelin-1 (3 x 10(-8) mol/l)-induced contractions in the aortic rings from SHR with but not without endothelium. The thromboxane A2 synthetase inhibitors OKY-046 (10(-5) mol/l) and RS-5186 (10(-5) mol/l) did not attenuate the contractions either with or without endothelium. Endothelin-1 significantly increased the release of 6-keto-prostaglandin F1 alpha, which is the metabolite of prostaglandin I2 and its precursor prostaglandin H2, from rings with endothelium of SHR, but the concentration of thromboxane B2 from aortic rings was unchanged. In the rings without endothelium the endothelin-1-induced release of 6-keto-prostaglandin F1 alpha was also observed. The half-maximal effective concentration of endothelin-1 for rings from SHR was shifted to the right by ONO-3708, but that of WKY rats was not changed, and significantly greater amounts of 6-keto-prostaglandin F1 alpha were released in the rings from SHR than in those from WKY rats by endothelin-1. CONCLUSIONS: Endothelin-1 induced the release of prostaglandin H2 from endothelial cells in the rat aorta, the effect being greater in the hypertensive state. The released prostaglandin H2, an endothelium-derived contracting factor, modulated the vasoconstriction that is induced by endothelin-1, another endothelium-derived contracting factor, in addition to the direct vasoconstrictive action of endothelin-1 on vascular smooth muscle.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Decreased muscle GLUT-4 and contraction-induced glucose transport after eccentric contractions.

Eccentric exercise causes muscle damage and decreased muscle glycogen and glucose transporter isoform (GLUT-4) protein content. We investigated whether the contraction-induced increase in skeletal muscle glucose transport and muscle performance is affected by prior eccentric contractions. The calf muscles from rats were stimulated for eccentric (EC) or concentric (CC) contractions or were passively stretched (ST). Muscles from unstimulated control (CT) rats were also studied. Two days later, all rats had their isolated hindlimbs perfused either at rest or during 15 min of isometric muscle contractions. EC rats had a significantly lower total GLUT-4 protein content in the white gastrocnemius (GW) muscle (55%) and red gastrocnemius (GR) muscle (34%) compared with muscle from the CT, ST, and CC rats. In contrast, GLUT-1 protein content was approximately twofold higher in the GW muscle in EC rats than in CT rats. In the GW and GR muscle, prior eccentric exercise decreased contraction-induced stimulation of glucose transport compared with CT, ST, and CC rats despite no difference in tension development and oxygen uptake among the groups. There was no change in total GLUT-4 content and glucose transport in the soleus (S) muscle among the four group. It is concluded that the GLUT-4 and GLUT-1 protein contents in fast-twitch muscle are decreased and increased, respectively, 2 days after eccentric contractions. The functional consequence of these changes appears to be decreased contraction-induced increase in skeletal muscle glucose transport.

Animals↗
PubMed1989

Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin: evidence for a role of G/F-actin transition in smooth muscle contraction.

The effect of botulinum C2 toxin was studied on the contractions of the guinea pig ileum myenteric plexus longitudinal muscle preparation. Botulinum C2 toxin inhibited the muscle contraction induced by electrical stimulation (60 V; 0.5 ms; 0.33 Hz) in a time and concentration dependent manner. The inhibitory effect occurred with a time lag of about 1 h, and depended on the presence of both toxin components. After 4 h of incubation with 1.7 micrograms/ml of component I and 6.7 micrograms/ml of component II of botulinum C2 toxin, the smooth muscle contraction was inhibited by about 60%. At these toxin concentrations, about 55% of the modifiable smooth muscle actin was ADP-ribosylated. Smooth muscle contraction induced by bradykinin and bethanechol were similarly inhibited. Moreover, the C2 toxin inhibited muscle contraction induced by Ba2+, and by direct muscle membrane depolarization (60 V; 10 ms; 0.33 Hz) after suppression of acetylcholine release by normorphine. Also cytochalasin D inhibited the electrically evoked contraction of the ileum longitudinal muscle. In contrast to botulinum C2 toxin, inhibition of contractility by cytochalasin D occurred without a lag phase, and was reversed by washing off the toxin. In contrast of guinea pig ileum longitudinal muscle, botulinum C2 toxin did not reduce the contraction of the rabbit aortic smooth muscle stimulated by K+-depolarization or noradrenaline.

Actins↗
PubMed1982

Dopamine produces muscle contractions and modulates motoneuron-induced contractions in Aplysia gill.

1. Dopamine has been reported to exist in unusually large quantities in Aplysia gill. The physiological role of this neurotransmitter in this organ was examined. 2. The addition of dopamine to a gill perfusate results in the contractions of the lateral and medial external pinnule muscles, the circular and longitudinal muscles of the afferent vessel, and the circular muscles of the efferent vessel. 3. Dopamine-induced contractions persist after chemical synaptic transmission is eliminated in the gill. This suggests that excitatory dopamine receptors are present on gill smooth muscle fibers themselves. 4. Dopamine also potentiates the gill response to action potentials in single identified gill motoneurons. Evidence presented suggests that muscle contractions and modulation of motoneuron contractions are independent phenomena. 5. While modulation may in part be mediated by increases in excitatory junction potential (EJP) amplitude, in many cases large increases in muscle contractions occur while the enhancement of EJPs is disproportionately small. 6. Dopamine's ability to produce muscle contractions suggests that there may be dopaminergic motoneuron innervation of the gill. We suggest that dopamine's modulatory actions may be mediated via modification of excitation-contraction coupling in smooth muscle fibers.

Animals↗
PubMed2003

Recruitment gain of antagonistic motoneurons is higher during lengthening contraction than during shortening contraction in man.

The purpose of this study was to investigate how the recruitment gain, as derived from the Hoffmann (H)-reflex measurement, of antagonistic motoneurons is modulated during voluntary lengthening (LEN) and shortening (SHO) contractions in the human tibialis anterior (TA) muscle. To this end, the parameters of the ratios of the slope in each ascending part of the H and M recruitment curves (Hslp/Mslp) in the antagonist muscle were compared between LEN and SHO contractions in nine young, healthy subjects. Although there were no differences in the levels of background activity (BGA) between LEN and SHO contractions in the agonist (TA) and antagonist (soleus) muscles, the Hslp/Mslp of the antagonist muscle was significantly higher during LEN contractions than during SHO contractions (P<0.01). It was therefore demonstrated that the recruitment gain of the antagonistic motoneurons to the la afferent inputs was higher during LEN contractions than during SHO contractions despite similar BGA levels. This result might reflect differences in the extent of the reciprocal inhibition from the agonist to the antagonist muscles and/or in the neural mechanism underlying the length-changing manners of the antagonist muscle itself.

Adult↗
PubMed2002

Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle.

The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein during 5 h of one-legged knee extensor exercise at 40 % of maximal work capacity and the NEFA kinetics, oxidation and rate of incorporation into intramuscular triacylglycerol (mTAG) were determined for the exercising and the non-exercising legs. During 4 h of one-legged knee extensor exercise, mTAG content decreased by 30 % (P < 0.05) in the contracting muscle, whereas it was unchanged in the non-contracting muscle. The uptake of plasma NEFA, as well as the proportion directed towards oxidation, was higher in the exercising compared to the non-exercising leg, whereas the rate of palmitate incorporation into mTAG was fourfold lower (0.70 +/- 0.14 vs. 0.17 +/- 0.04 micromol (g dry wt)(-1) h(-1); P < 0.05), resulting in fractional synthesis rates of 1.0 +/- 0.2 and 3.8 +/- 0.9 % h(-1) (P < 0.01) for the contracting and non-contracting muscle, respectively. These findings demonstrate that mTAG in human skeletal muscle is continuously synthesised and degraded and that the metabolic fate of plasma NEFA entering the muscle is influenced by muscle contraction, so that a higher proportion is directed towards oxidation at the expense of storage in mTAG.

Adult↗
PubMed1987

Calcium channels and excitation-contraction coupling in cardiac cells. II. A pharmacological study of the biphasic contraction in guinea-pig papillary muscle.

Biphasic contractions were obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) in the presence of 0.3 microM isoproterenol. Mn2+ ions inhibited the two components of contraction in a similar way. Nifedipine and particularly Cd2+ ions specifically inhibited the second component of contraction. Isoproterenol and BAY K 8644 markedly increased the amplitude of the second component (P2) of contraction. Nevertheless, a moderate positive inotropic effect of isoproterenol was found on the first component (P1) of contraction when excitability was restored by 0.2 mM Ba instead of isoproterenol. Acetylcholine and hypoxia decreased the amplitude of the second component of contraction to a greater extent. In the presence of digoxin or Na+-free solution, P1 was strongly increased. When sarcoplasmic reticular function was hindered by 1mM caffeine or in the presence of Ca2+-free Sr2+ solution, digoxin always induced a negative inotropic effect on P2. Inversely in these conditions the transient positive inotropic effect of Na+-free solution was strongly reduced. These results are consistent with the hypothesis that the late component of contraction is triggered by the slow inward Ca2+ current and that the early component is due to Ca2+ release from the sarcoplasmic reticulum.

Acetylcholine↗
PubMed1992

Slow channel calcium blockers attenuate reoxygenation-mediated vascular contraction, but augment anoxia-mediated vascular contraction.

Anoxia and reoxygenation modulate vasomotor tone. To determine the effect of the slow channel calcium blockers verapamil and diltiazem in vascular smooth muscle contraction during states of altered oxygenation, rat aortic rings with intact endothelium were contracted with norepinephrine (NE) or the thromboxane A2 mimic U46,619 and then exposed abruptly to anoxia (switch from 95% O2 to 95% N2) for 30 min and then reoxygenated (switch from 95% N2 to 95% O2). Anoxia caused a transient 40 +/- 9% (mean +/- SE, n = 15) increase in contraction, whereas reoxygenation resulted in an initial decrease followed by a large (83 +/- 21%) increase in contraction. Treatment of vascular rings with verapamil or diltiazem (1 microgram/ml or 2 microM) decreased contractile response to the agonists (p less than 0.01). Both these agents consistently augmented the magnitude and duration of anoxia-induced contraction (p less than 0.01). In other experiments, pretreatment of vascular rings with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, or with oxyhemoglobin, an inhibitor of EDRF activity, or de-endothelialization resulted in marked (p less than 0.01) decrease in anoxic contraction, indicating that anoxia-induced contraction is caused by modulation of EDRF. Treatment of aortic rings with verapamil also reduced acetylcholine-mediated relaxation (from 86 +/- 6% to 45 +/- 5%, p less than 0.02) and cyclic GMP accumulation (from 192 +/- 53 to 111 +/- 35 fmol/mg, p less than 0.02), indicating reduction in EDRF synthesis or activity by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Effect of endothelin-1 on spontaneous contractions and effects of nimodipine and isradipine on endothelin-1-induced contractions in myometrial strips isolated from normal pregnant and preeclamptic women.

BACKGROUND: To examine the effect of endothelin-1 (ET-1) on spontaneous contractile activity and the effects of nimodipine and isradipine on ET-1-induced contractile responses in myometrial strips isolated from normal pregnant and preeclamptic women. MATERIAL AND METHODS: . Isolated myometrial strips were obtained from seven normal pregnant and seven preeclamptic women undergoing elective cesarean section and the strips were mounted in organ baths for recording of isometric tension. The effect of increasing concentration of ET-1 on spontaneous contractions and effects of increasing concentration of nimodipine and isradipine on ET-1-induced contractions were recorded. RESULTS: ET-1 dose-dependently (10(-11)-10(-8) M) increased the amplitude and frequency of spontaneous contractions in all myometrial strips obtained from normal pregnant and preeclamptic women. The increase in the amplitude of contractions in preeclamptic strips was significantly higher than that of normal strips. The increase in amplitude of contractions in normal and preeclamptic strips reached statistical significance beginning from the concentrations of 10(-9) M and 10(-11) M, respectively. ET-1 (10(-8) M) also increased the basal tone of all myometrial strips isolated from normal pregnant and preeclamptic women. When ET-1 (10(-8) M)-contracted myoinetrial strips were exposed to increasing concentrations of nimodipine (10(-6)-3x10(-5)M) and isradipine (10(-5)-3x10(-4) M), nimodipine and isradipine dose-dependently decreased the amplitude and frequency of contractions. CONCLUSIONS: The increase in contractile response with ET-1 was significantly higher in myometrial strips isolated from preeclamptic women compared to those of myometrial strips isolated from normal pregnant women. These increases in contractile response are at least in part mediated by dihydropyridine-sensitive calcium channels, since they were significantly reduced in the presence of increasing concentrations of nimodipine and isradipine.

Calcium Channel Blockers↗
PubMed1995

A mechanochemical model for adult dermal wound contraction and the permanence of the contracted tissue displacement profile.

The healing of adult mammalian skin wounds involves a complex sequence of spatially and temporally coordinated processes. Wound contraction, by reducing the size of the injury, is an intrinsic component of full-thickness excisional dermal wound healing. The underlying biomechanics of wound contraction, however, are not fully understood, and little is known about the pathogenesis of severe medical conditions known as fibrocontractive diseases. The aim of this work is to investigate a deterministic mathematical model in order to obtain insight into the mechanistic relationships between wound contraction and associated normal and pathological healing processes. The model describes the essential roles of fibroblast and myofibroblast cells, a chemical growth factor and the extracellular matrix which includes type I collagen. The model results are qualitatively consistent with the biology of fibroplasia and wound contraction. It is shown that a contracted state evolves during a (long) transient phase of healing known as "proliferation", while collagen kinetics are fundamental to the considerably longer "remodelling" phase. Some quantitative results, notably on the evolution of wound contraction, compare favourably with experimental data. Application of the model to adult human dermal wound healing in vivo, with a greater understanding of the underlying biological mechanisms involved, may suggest strategies for controlling contraction and fibrocontractive diseases.

Adult↗
PubMed1991

Stopped-flow measurement of cytoskeletal contraction: Dictyostelium myosin II is specifically required for contraction of amoeba cytoskeletons.

Cytoskeletons provide valuable information on the composition and organization of the cell's contractile machinery, and in many cases these cell models retain the ability to contract. To quantitate contraction rates, we developed a novel stopped-flow assay permitting simultaneous analysis of thousands of Dictyostelium cytoskeletons within milliseconds of mixing with Mg-ATP. Cytoskeletons were placed in one syringe of the stopped flow apparatus and the appropriate buffer was placed in the second syringe. Mixing with Mg-ATP caused an immediate increase in the absorbance at 310 nm. Rapid fixation of the cytoskeletons during the reaction confirmed that this change in absorbance was highly correlated with contraction of the cytoskeletons. This spectroscopic change was used to measure the effects of temperature, pH, ionic strength, and nucleotides on contraction rate. Treatment with high salt and ATP removed most of the myosin, some actin, and small amounts of minor proteins. These extracted cytoskeletons lost the ability to contract, but after the addition of purified Dictyostelium myosin they regained full function. In contrast, rabbit skeletal muscle myosin was unable to restore contractility, even though it bound to the extracted cytoskeletons. Cytoskeletons prepared from a myosin-null mutant did not contract. Upon the addition of purified ameba myosin, however, they became contractile. These results suggest that filamentous Dictyostelium myosin II is essential for contraction, and that the actin cytoskeleton and associated proteins retain their functional organization in the absence of myosin.

Adenosine Triphosphate↗
PubMed1995

Contraction potency of hypertrophic scar-derived fibroblasts in a connective tissue model: in vitro analysis of wound contraction.

Many investigators have reported that collagen gel contraction reflects the mechanism of wound contraction. By using a connective tissue model (CTM) of collagen gel lattice, we analyzed the contraction potency of fibroblasts that had been obtained from hypertrophic scar, normal skin, and normal oral mucosa. We then tried to analyze the mechanism of CTM contraction by immunofluorescent microscopic and transmission electron microscopic examinations. Hypertrophic scar-derived fibroblasts in CTM possessed the greatest contraction potency and the shortest lag time when compared with those of normal skin and normal oral mucosa-derived CTMs. It became clear that the initial contractive degree of CTM was closely related to morphological changes of fibroblast cells into bipolar and elongated shapes. Hypertrophic scar-derived fibroblasts elongated their processes faster, and their intracellular actin filaments were more numerous than those of normal fibroblasts. We believe that the hypertrophic scar-derived CTM is a useful pathological model for the research of wound contraction and hypertrophic scar formation.

Adolescent↗
PubMed2001

Contraction of fibroblast-containing collagen gels: initial collagen concentration regulates the degree of contraction and cell survival.

Remodeling of extracellular matrix involves a number of steps including the recruitment, accumulation, and eventual apoptosis of parenchymal cells as well as the production, organization, and rearrangement of extracellular matrix produced by these cells. The culture of fibroblasts in three-dimensional gels made of type I collagen has been used as a model of tissue contraction which characterizes both wound repair and fibrosis. The current study was designed to determine the effect of initial collagen concentration on the ability of fibroblasts to contract collagen gels and on cell survival. Native type I collagen was extracted from rat tail tendons and used to prepare collagen gels with varying collagen concentrations (0.75-2.0 mg/ml). Human lung fibroblasts (HFL-1) were cast into the gels and cultured in Dulbecco modified Eagle medium with 0.1% fetal calf serum for 2 wk. The gel size, collagen content, and deoxyribonucleic acid (DNA) content were determined. Gels prepared with an initial concentration of 0.75 mg/ml contracted more rapidly and to a smaller final size than gels prepared from 2 mg/ml initial collagen concentration (final size 7.1 versus 36.4% of initial size, P < 0.01). There was no significant degradation of the collagen in the gels under either condition. Hence, the dramatically increased contraction of the lower density gels resulted in a higher final density (P < 0.01). Cell density was estimated from DNA content. In low initial density gels, the final DNA content was significantly less than that in higher initial density gels (0.73 versus 1.88 microg/gel, P < 0.05). This was accompanied by an increased percentage of apoptotic cells at day 14 (43.3 versus 34.1%, P < 0.05). If the gels were maintained in the attached state which largely prevents contraction, apoptosis was significantly reduced, suggesting that contraction rather than matrix composition was a requirement for the increased apoptosis. In summary, these findings indicate that the initial matrix composition can lead to differing outcomes during fibroblast-mediated wound contraction.

Apoptosis↗