Backward movements of cross-bridges by application of stretch and by binding of MgADP to skeletal muscle fibers in the rigor state as studied by x-ray diffraction.
(65/15397)
The effects of the applied stretch and MgADP binding on the structure of the actomyosin cross-bridges in rabbit and/or frog skeletal muscle fibers in the rigor state have been investigated with improved resolution by x-ray diffraction using synchrotron radiation. The results showed a remarkable structural similarity between cross-bridge states induced by stretch and MgADP binding. The intensities of the 14.4- and 7.2-nm meridional reflections increased by approximately 23 and 47%, respectively, when 1 mM MgADP was added to the rigor rabbit muscle fibers in the presence of ATP-depletion backup system and an inhibitor for muscle adenylate kinase or by approximately 33 and 17%, respectively, when rigor frog muscle was stretched by approximately 4.5% of the initial muscle length. In addition, both MgADP binding and stretch induced a small but genuine intensity decrease in the region close to the meridian of the 5.9-nm layer line while retaining the intensity profile of its outer portion. No appreciable influence was observed in the intensities of the higher order meridional reflections of the 14.4-nm repeat and the other actin-based reflections as well as the equatorial reflections, indicating a lack of detachment of cross-bridges in both cases. The changes in the axial spacings of the actin-based and the 14.4-nm-based reflections were observed and associated with the tension change. These results indicate that stretch and ADP binding mediate similar structural changes, being in the correct direction to those expected for that the conformational changes are induced in the outer portion distant from the catalytic domain of attached cross-bridges. Modeling of conformational changes of the attached myosin head suggested a small but significant movement (about 10-20 degrees) in the light chain-binding domain of the head toward the M-line of the sarcomere. Both chemical (ADP binding) and mechanical (stretch) intervensions can reverse the contractile cycle by causing a backward movement of this domain of attached myosin heads in the rigor state. (+info)
Role of Ca2+ and cross-bridges in skeletal muscle thin filament activation probed with Ca2+ sensitizers.
(66/15397)
Thin filament regulation of contraction is thought to involve the binding of two activating ligands: Ca2+ and strongly bound cross-bridges. The specific cross-bridge states required to promote thin filament activation have not been identified. This study examines the relationship between cross-bridge cycling and thin filament activation by comparing the results of kinetic experiments using the Ca2+ sensitizers caffeine and bepridil. In single skinned rat soleus fibers, 30 mM caffeine produced a leftward shift in the tension-pCa relation from 6.03 +/- 0.03 to 6.51 +/- 0.03 pCa units and lowered the maximum tension to 0.60 +/- 0.01 of the control tension. In addition, the rate of tension redevelopment (ktr) was decreased from 3.51 +/- 0.12 s-1 to 2.70 +/- 0.19 s-1, and Vmax decreased from 1.24 +/- 0.07 to 0.64 +/- 0.02 M.L./s. Bepridil produced a similar shift in the tension-pCa curves but had no effect on the kinetics. Thus bepridil increases the Ca2+ sensitivity through direct effects on TnC, whereas caffeine has significant effects on the cross-bridge interaction. Interestingly, caffeine also produced a significant increase in stiffness under relaxing conditions (pCa 9.0), indicating that caffeine induces some strongly bound cross-bridges, even in the absence of Ca2+. The results are interpreted in terms of a model integrating cross-bridge cycling with a three-state thin-filament activation model. Significantly, strongly bound, non-tension-producing cross-bridges were essential to modeling of complete activation of the thin filament. (+info)
Effects of temperature and preservation time on the pharmacological response of isolated vascular endothelial and smooth muscle function.
(67/15397)
In clinical transplantation and cardiovascular surgery, cold preservation is usually used because it is a simple method. However, the established temperature is by no means exact. The aim of this study was to find the optimum storage temperature for preservation of the vasculature by observing the pharmacological endothelium and smooth muscle response. The thoracic aorta of 36 male Wister rats were studied in organ baths: as fresh control after 24 hours, 48 hours and 72 hours of storage at 0.5 degree C, 4 degrees C and 8 degrees C in Krebs-Henseleit bicarbonate (KHB) solution. Acetylcholine (Ach) was used to elicit endothelium-dependent relaxation, and sodium nitroprusside (SNP) to elicit smooth muscle-dependent relaxation. The contractility caused by Phenylephrine (Ph) was influenced by time but before 48 hours it was not influenced by preservation temperature. Significant responsive deterioration by Ach and SNP was seen after 24 hours of storage at 0.5 degree C as compared with storage at 4 degrees C. The endothelium-dependent relaxing function and smooth muscle-dependent relaxing function were best preserved at 4 degrees C and 8 degrees C. These results indicate that precise temperature control is necessary for vessel preservation in clinical situations. (+info)
Regulation of Limulus skeletal muscle contraction.
(68/15397)
Skeletal muscle contraction of Limulus polyphemus, the horseshoe crab, seemed to be regulated in a dual manner, namely Ca2+ binding to the troponin complex as well phosphorylation of the myosin light chains (MLC) by a Ca2+/calmodulin-dependent myosin light chain kinase. We investigated muscle contraction in Limulus skinned fibers in the presence of Ca2+ and of Ca2+/calmodulin to find out which of the two mechanisms prevails in Limulus skeletal muscle contraction. Although skinned fibers revealed high basal MLC mono- and biphosphorylation levels (0.48 mol phosphate/mol 31 kDa MLC; 0.52 mol phosphate/mol 21 kDa MLC), the muscle fibers were fully relaxed at pCa 8. Upon C2+ or Ca2+/calmodulin activation, the fibers developed force (357+/-78.7 mN/mm2; 338+/-69.7 mN/mm2, respectively) while the MLC phosphorylation remained essentially unchanged. We conclude that Ca2+ activation is the dominant regulatory mechanism in Limulus skeletal muscle contraction. (+info)
Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.
(69/15397)
Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. (+info)
Neuromyotonia: an unusual presentation of intrathoracic malignancy.
(70/15397)
A 48 year old woman is described who presented with increasing muscular rigidity and who was found to have a mediastinal tumour. Electrophysiological studies revealed that the muscular stiffness resulted from very high frequency motor unit activity which outlasted voluntary effort, and which was abolished by nerve block. The abnormal activity may have arisen at the anterior horn cell level. Marked improvement followed the administration of diphenylhydantoin. (+info)
Measurements of muscle strength and performance in children with normal and diseased muscle.
(71/15397)
A study has been made of two simple means of measuring muscle power in children with normal and diseased muscle. In one the length of time that the leg and the head could be held at 45 degrees above the horizontal was measured with the child supine. In the second, measurements were made of the isometric strength of six muscle groups with the newly developed Hammersmith Myometer. In the timed performance tests only 5 (8%) of a group of 61 children known to have muscle disease achieved the minimum expected values for their ages. Myometer readings of the isometric power of the children with muscle disease also have values which were below those of a comparable group of normal children. The reproducibility of muscle strength measurements in young children has been shown to be good, whereas the timed performance tests, though able to differentiate normal children from children with muscle disease, did not show sufficient reporducibility for this test to be recommended for sequential measurements. (+info)
Primitive nervous systems: electrophysiology of the pharynx of the polyclad flatworm, Enchiridium punctatum.
(72/15397)
1. Electrical activity accompanying motor activity can be recorded from the excised pharynx of Enchiridium punctatum. Multiple stimuli elicit behaviour which consists of an initial aperture closure followed by extension and then peristalsis. If the stimulus parameters are increased the preparation bends from side to side instead of proceeding through the behavioural sequence. Bending appears to inhibit other movements differentially. 2. The conduction involved with peristalsis is polarized and proceeds in a proximal direction. 3. With stimulus intensities greater than those needed to produce the behavioural response an initial muscle potential (IMP) is evoked. The IMP is frequency sensitive. Maximum facilitation occurs within 100 ms and drops to 50% of maximum within 250 ms. 4. Conduction velocities of the IMP range from 0-05 m s-1 to 1-9 m s-1. Conduction velocities appear to increase with facilitation. (+info)