ATP hydrolysis during contraction of permeabilized airway smooth muscle.
(49/2703)
This study determined whether the time-dependent decline in the rate of ATP hydrolysis by actomyosin ATPase during sustained isometric force can occur in the absence of a time-dependent decline in regulatory myosin light chain (rMLC) phosphorylation in Triton X-100-permeabilized canine tracheal smooth muscle. Maximal activation with 10 microM Ca(2+) induced sustained increases in isometric force, stiffness, and rMLC phosphorylation; however, the increase in the ATP hydrolysis rate was initially high but then declined to a steady-state level above that of the unstimulated muscle (basal 31.8 +/- 5.8 nmol. cm(-3). s(-1); peak 81.4 +/- 11.3 nmol. cm(-3). s(-1); steady-state 62.2 +/- 9.1 nmol. cm(-3). s(-1)). Activation of strips in which the rMLC was irreversibly and maximally thiophosphorylated with adenosine 5'-O-(3-thiotriphosphate) also induced sustained increases in isometric force and stiffness but a nonsustained increase in ATP hydrolysis rate. There was no significant difference in the peak or steady-state isometric force, stiffness, or ATP hydrolysis rate or in the steady-state maximum unloaded shortening velocity between strips activated by 10 microM Ca(2+) or rMLC thiophosphorylation (0.058 +/- 0.016 and 0.047 +/- 0.011 muscle lengths/s, respectively). Mechanisms other than changes in rMLC phosphorylation contribute to the time-dependent decline in actomyosin ATPase activity during sustained activation of canine tracheal smooth muscle. (+info)
Regeneration of new fibers in muscles of old rats reduces contraction-induced injury.
(50/2703)
Skeletal muscles are injured by their own contractions. Compared with muscles in young animals, those in old animals are injured more easily and more severely and regenerate less well afterward. Injection of a myotoxin (bupivacaine) causes complete degeneration of fibers in extensor digitorum longus (EDL) muscles of rats, followed by full regeneration within 60 days. We tested the specific hypothesis that, 3 days after a protocol of pliometric (lengthening) contractions, the newly regenerated muscle fibers in bupivacaine-treated EDL muscles in both young and old rats would show a lesser deficit in maximum force and fewer damaged fibers than muscles in nontreated EDL muscles. The treated and nontreated EDL muscles of young and old male Wistar rats were administered a protocol of 225 pliometric contractions and were evaluated 3 days afterward, when morphological damage to muscle fibers is most severe. In treated compared with nontreated EDL muscles of both young and old rats, the force deficit and the number of damaged fibers were each reduced by approximately 75%. We conclude that newly regenerated fibers in muscles of young and old animals are resistant to injury and that maintenance of newly regenerated fibers by conditioning may prevent inadvertent damage, particularly in muscles of elderly people. (+info)
Analysis of the atypical characteristics of adenosine receptors mediating negative inotropic and chronotropic responses of guinea-pig isolated atria and papillary muscles.
(51/2703)
1. Adenosine receptor(s) mediating negative inotropy of paced left atria, isoprenaline-stimulated paced left atria and papillary muscles, and negative chronotropy of spontaneously beating right atria were characterized. 2. Isometric tension of guinea-pig isolated paced left atria and left ventricular papillary muscles and rate of contraction of spontaneously beating right atria were recorded. Papillary muscles were pre-stimulated with isoprenaline (1x10-8 M). Concentration-response curves (CRCs) for tension or rate reduction by N6-cyclopentyladenosine (CPA), the stereoisomers of N6-(2-phenylisopropyl)adenosine ((+)-PIA and (-)-PIA), 5'-(N-carboxamido)adenosine (NECA), N6-2-(4-aminophenyl)ethyladenosine (APNEA) and N6-(3-iodobenzyl)adenosine-5'-N-methyuromide (IB-MECA) revealed a potency order of CPA=(-)-PIA>NECA in right atria and papillary muscles, which is consistent with involvement of A1-receptors. The potency order in left atria was CPA=NECA>(-)-PIA>(+)-PIA>APNEA, which is not typical of A1 adenosine receptors. Weak activity of APNEA and IB-MECA discounts involvement of A3 receptors. 3. pA2 values for the antagonism of CPA by 8(p-sulfophenyl)theophylline (8-SPT) were calculated from Schild plots (log concentration-ratio against log 8-SPT concentration), the unity slopes of which indicated competitive antagonism. The pA2 value in the papillary muscles was significantly higher than for atrial preparations, indicating a possible difference in receptor characteristics between atrial and papillary muscle responses. 4. In left and right atria there was a limit to the displacement of the CPA CRCs at higher concentrations of 8-SPT. The 8-SPT-resistant component of the response is suggested to arise from duality of coupling of a common A1 receptor through either different G proteins or G protein subunits to independent transduction pathways. The results with papillary muscles can be explained by a typical A1 receptor coupled to a single transduction pathway. (+info)
Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure.
(52/2703)
1. Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved. 2. We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles. 3. Untreated MI rats had significant LV dilatation (10.6+/-0.4* vs 8.9+/(-0.3) mm, MI vs control), impaired systolic function (fractional shortening=11+/-2* vs 38+/-2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6+/(-0.5) mm) and systolic function (13+/(-2%). The propranolol treated animals had higher LV end-diastolic pressures (27+/-2* vs 20+/(-3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6+/(-0.3) vs 2.4+/(0.5 g mm(-2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6+/(-0.3 g mm(-2) or the duration of Ca transients during isoproterenol stimulation. 4. Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium. (+info)
The force bearing capacity of frog muscle fibres during stretch: its relation to sarcomere length and fibre width.
(53/2703)
1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria were tetanized (0.9-1.8 C) while a marked ( approximately 1 mm) segment was held at constant length by feedback control. Force enhancement was produced by applying a controlled stretch ramp to the fibre segment during the tetanus plateau, the steady force reached during stretch being used as a measure of the maximum force that the myosin cross-bridges can hold before they detach. 2. The amplitude of force enhancement during stretch did not vary in proportion to the isometric force as the sarcomere length was changed, maximum force enhancement being attained near 2.4 microm sarcomere length compared with 2.0 microm for the isometric force. 3. The influence of fibre width on the force enhancement-sarcomere length relationship was evaluated by normalizing force enhancement to the tetanic (pre-stretch) force in this way allowing for the differences in myofilament overlap at the various lengths. The amplitude of force enhancement (normalized to the tetanic force) increased by approximately 70 % as the relative width of the myofilament lattice was reduced from a nominal value of 1.05 at a sarcomere length of 1.8 microm to 0.85 at a sarcomere length of 2.8 microm. 4. Changes in fibre width equivalent to those produced by altering the sarcomere length were produced by varying the tonicity of the extracellular medium. Force enhancement, normalized to the control isometric force at each tonicity, exhibited a width dependence that agreed well with that described in the previous point. Stretch ramps applied to frog skinned muscle fibres during calcium-induced contracture likewise resulted in a greater force enhancement during stretch after reducing the fibre width by osmotic compression. 5. The results suggest that the strength of binding of the myosin cross-bridges, unlike the isometric force, varies with the lateral distance between the myofilaments. (+info)
F-actin stabilization increases tension cost during contraction of permeabilized airway smooth muscle in dogs.
(54/2703)
1. Dynamic actin reorganization involving actin polymerization and depolymerization may play an important functional role in smooth muscle. 2. This study tested the hypothesis that F-actin stabilization by phalloidin increases tension cost (i.e. ATP hydrolysis rate per unit of isometric force) during Ca2+-induced activation of Triton X-100-permeabilized canine tracheal smooth muscle. 3. Adenosine 5'-triphosphate (ATP) hydrolysis rate was quantified using an enzyme-coupled NADH fluorometric technique, regulatory myosin light chain (rMLC) phosphorylation was measured by Western blot analysis, and maximum unloaded shortening velocity (Vmax) was estimated by interpolation of the force-velocity relationship to zero load during isotonic loading. 4. Maximal activation with 10 microM free Ca2+ induced sustained increases in isometric force, stiffness, and rMLC phosphorylation. However, the increase in ATP hydrolysis rate initially reached peak values, but then declined to steady-state levels above that of the unstimulated muscle. Thus, tension cost decreased throughout steady-state isometric force. 5. Following incubation of permeabilized strips with 50 microM phalloidin for 1 h, the increases in isometric force and stiffness were not sustained despite a sustained increase in rMLC phosphorylation. Also, after an initial decline, tension cost increased throughout activation. Phalloidin had no effect on Vmax during steady-state isometric force or on rMLC phosphorylation. 6. These findings suggest that dynamic reorganization of actin is necessary for optimal energy utilization during contraction of permeabilized airway smooth muscle. (+info)
Tropomyosin modulates pH dependence of isometric tension.
(55/2703)
We investigated the effect of pH on isometric tension in actin filament-reconstituted and thin filament-reconstituted bovine cardiac muscle fibers in the pH range of 6.0-7.4. Thin filament was reconstituted from purified G-actin with either bovine cardiac tropomyosin (Tm) or rabbit skeletal Tm in conjunction with cardiac or skeletal troponin (Tn). Results showed that isometric tension decreased linearly with a decrease in pH. The slope of the pH-tension relation, DeltaF/DeltapH (Deltarelative tension/Deltaunit pH), was 0.28 and 0.44 in control cardiac fibers and skeletal fibers, respectively. In actin filament-reconstituted fibers without regulatory proteins, DeltaF/DeltapH was 0.62, namely larger than that in cardiac or skeletal fibers. When reconstituted with cardiac Tm-Tn complex (nTm), DeltaF/DeltapH recovered to 0.32, close to the value obtained in control cardiac fibers. When reconstituted with skeletal nTm, DeltaF/DeltapH recovered to 0.48, close to the value for control skeletal fibers. To determine whether Tm or Tn is responsible for the inhibitory effects of nTm on the tension decrease caused by reduced pH, thin filament was reconstituted with cardiac Tm and skeletal Tn, or with skeletal Tm and cardiac Tn. When cardiac Tm was used, pH dependence of isometric tension coincided with that of control cardiac fibers. When skeletal Tm was used, the pH dependence coincided with that of control skeletal fibers. Furthermore, closely similar results were obtained in fibers reconstituted with actin and either cardiac or skeletal Tm without Tn. These results demonstrate that Tm but not Tn modulates the pH dependence of active tension. (+info)
Is there a relationship between balance, gait performance and muscular strength in 75-year-old women?
(56/2703)
OBJECTIVE: To see if there is a relationship between clinical and laboratory tests of balance, muscular strength and gait in elderly women. DESIGN: A randomized population-based study. SETTINGS: Malmo, Sweden. METHODS: We investigated balance with a simple test of standing on one leg, as well as a computerized balance platform. Muscular strength was tested by computerized dynamometer. Extension and flexion of the knee and dorsiflexion of the ankle were tested. We measured the time and number of steps taken to walk a certain distance and the subjects' height and weight. PARTICIPANTS: 418 randomly selected 75-year-old women, of whom 230 took part. RESULTS: There was no relation between the computerized balance tests and any of the other tests. The non-computerized balance test was correlated with gait time and number of steps (r = -0.50, P<0.001 and r = -0.40, P<0.001, respectively). Tests of extension and flexion, strength of the knee and ankle dorsiflexion were related to gait, speed and number of steps. Heavy women had poorer balance when assessed by the non-computerized test (r = -0.32, P<0.001) and with the computerized, stable platform, eyes-open test (r = 0.27, P<0.001) and eyes-closed test (r = 0.44, P<0.001). The heavier an individual was, the slower her gait and the shorter her steps, despite having stronger knee muscles. CONCLUSION: There is no relationship between the simple balance tests and computerized platform tests. Muscle strength of the leg is not necessarily linked to balance, but rather to gait performance. (+info)