Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease. (1/1432)

Pulmonary hyperinflation impairs the function of the diaphragm in patients with chronic obstructive pulmonary disease (COPD). However, it has been recently demonstrated that the muscle can counterbalance this deleterious effect, remodelling its structure (i.e. changing the proportion of different types of fibres). The aim of this study was to investigate whether the functional impairment present in COPD patients can be associated with structural subcellular changes of the diaphragm. Twenty individuals (60+/-9 yrs, 11 COPD patients and 9 subjects with normal spirometry) undergoing thoracotomy were included. Nutritional status and respiratory function were evaluated prior to surgery. Then, small samples of the costal diaphragm were obtained and processed for electron microscopy analysis. COPD patients showed a mean forced expiratory volume in one second (FEV1) of 60+/-9% predicted, a higher concentration of mitochondria (n(mit)) in their diaphragm than controls (0.62+/-0.16 versus 0.46+/-0.16 mitochondrial transections (mt) x microm(-2), p<0.05). On the other hand, subjects with air trapping (residual volume (RV)/total lung capacity (TLC) >37%) disclosed not only a higher n(mit) (0.63+/-0.17 versus 0.43+/-0.07 mt x microm(-2), p<0.05) but shorter sarcomeres (L(sar)) than subjects without this functional abnormality (2.08+/-0.16 to 2.27+/-0.15 microm, p<0.05). Glycogen stores were similar in COPD and controls. The severity of airways obstruction (i.e. FEV1) was associated with n(mit) (r=-0.555, p=0.01), while the amount of air trapping (i.e. RV/TLC) was found to correlate with both n(mit) (r=0.631, p=0.005) and L(sar) (r=-0.526, p<0.05). Finally, maximal inspiratory pressure (PI,max) inversely correlated with n(mit) (r=-0.547, p=0.01). In conclusion, impairment in lung function occurring in patients with chronic obstructive pulmonary disease is associated with subcellular changes in their diaphragm, namely a shortening in the length of sarcomeres and an increase in the concentration of mitochondria. These changes form a part of muscle remodelling, probably contributing to a better functional muscle behaviour.  (+info)

Morphology and mechanics of tongue movement in the African pig-nosed frog Hemisus marmoratum: a muscular hydrostatic model. (2/1432)

The goal of this study was to investigate morphological adaptations associated with hydrostatic elongation of the tongue during feeding in the African pig-nosed frog Hemisus marmoratum. Whereas previous studies had suggested that the tongue of H. marmoratum elongates hydraulically, the anatomical observations reported here favour a muscular hydrostatic mechanism of tongue elongation. H. marmoratum possesses a previously undescribed compartment of the m. genioglossus (m. genioglossus dorsoventralis), which is intrinsic to the tongue and whose muscle fibres are oriented perpendicular to the long axis of the tongue. On the basis of the arrangement and orientation of muscle fibres in the m. genioglossus and m. hyoglossus, we propose a muscular hydrostatic model of tongue movement in which contraction of the m. genioglossus dorsoventralis, together with unfolding of the intrinsic musculature of the tongue, results in a doubling in tongue length. Electron micrographs of sarcomeres from resting and elongated tongues show that no special adaptations of the sarcomeres are necessary to accommodate the observed doubling in tongue length during feeding. Rather, the sarcomeres of the m. genioglossus longitudinalis are strikingly similar to those of anuran limb muscles. The ability to elongate the tongue hydrostatically, conferred by the presence of the m. genioglossus dorsoventralis, is associated with the appearance of several novel aspects of feeding behaviour in H. marmoratum. These include the ability to protract the tongue slowly, thereby increasing capture success, and the ability to aim the tongue in azimuth and elevation relative to the head. Compared with other frogs, the muscular hydrostatic system of H. marmoratum allows more precise, localized and diverse tongue movements. This may explain why the m. genioglossus of H. marmoratum is composed of a larger number of motor units than that of other frogs.  (+info)

Dynamic distribution and formation of a para-sarcomeric banding pattern of prosomes during myogenic differentiation of satellite cells in vitro. (3/1432)

Myogenesis proceeds by fusion of proliferating myoblasts into myotubes under the control of various transcription factors. In adult skeletal muscle, myogenic stem cells are represented by the satellite cells which can be cultured and differentiate in vitro. This system was used to investigate the subcellular distribution of a particular type of prosomes at different steps of the myogenic process. Prosomes constitute the MCP core of the 26S proteasomes but were first observed as subcomplexes of the untranslated mRNPs; recently, their RNase activity was discovered. A monoclonal antibody raised against the p27K subunit showed that the p27K subunit-specific prosomes move transiently into the nucleus prior to the onset of myoblast fusion into myotubes; this represents possibly one of the first signs of myoblast switching into the differentiation pathway. Prior to fusion, the prosomes containing the p27K subunit return to the cytoplasm, where they align with the gradually formed lengthwise-running desmin-type intermediate filaments and the microfilaments, co-localizing finally with the actin bundles. The prosomes progressively form discontinuous punctate structures which eventually develop a pseudo-sarcomeric banding pattern. In myotubes just formed in vitro, the formation of this pattern seems to preceed that produced by the muscle-specific sarcomeric (alpha)-actin. Interestingly, this pattern of prosomes of myotubes in terminal in vitro differentiation was very similar to that of prosomes observed in vivo in foetal and adult muscle. These observations are discussed in relation to molecular myogenesis and prosome/proteasome function.  (+info)

Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells that express beta-tropomyosin. (4/1432)

We compared the dynamics of the contraction and relaxation of single myocytes isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-beta-Tm) mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared with NTG controls, TG-beta-Tm myocytes showed significantly reduced maximal rates of contraction and relaxation with no change in the extent of shortening. This result indicated that the depression in contraction dynamics determined in TG-beta-Tm isolated hearts is intrinsic to the cells. To further investigate the effect of Tm isoform switching on myofilament activity and regulation, we measured myofilament force and ATPase rate as functions of pCa (-log of [Ca2+]). Compared with controls, force generated by myofilaments from TG-beta-Tm hearts and myofibrillar ATPase activity were both more sensitive to Ca2+. However, the shift in pCa50 (half-maximally activating pCa) caused by changing sarcomere length from 1.8 to 2.4 microm was not significantly different between NTG and TG-beta-Tm fiber preparations. To test directly whether isoform switching affected the economy of contraction, force versus ATPase rate relationships were measured in detergent-extracted fiber bundles. In both NTG and TG-beta-Tm preparations, force and ATPase rate were linear and identically correlated, which indicated that crossbridge turnover was unaffected by Tm isoform switching. However, detergent extracted fibers from TG-beta-Tm demonstrated significantly less maximum tension and ATPase activity than NTG controls. Our results provide the first evidence that the Tm isoform population modulates the dynamics of contraction and relaxation of single myocytes by a mechanism that does not alter the rate-limiting step of crossbridge detachment. Our results also indicate that differences in sarcomere-length dependence of activation between cardiac and skeletal muscle are not likely due to differences in the isoform population of Tm.  (+info)

Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments. (5/1432)

Myofibrillogenesis in situ was investigated by confocal microscopy of immunofluorescently labelled whole mount preparations of early embryonic chicken heart rudiments. The time-course of incorporation of several components into myofibrils was compared in triple-stained specimens, taken around the time when beating starts. All sarcomeric proteins investigated so far were already expressed before the first contractions and myofibril assembly happened within a few hours. No typical stress fibre-like structures or premyofibrils, structures observed in cultured cardiomyocytes, could be detected during myofibrillogenesis in the heart. Sarcomeric proteins like (&agr;)-actinin, titin and actin were found in a defined localisation pattern even in cardiomyocytes that did not yet contain myofibrils, making up dense body-like structures. As soon as the heart started to beat, all myofibrillar proteins were already located at their exact position in the sarcomere. The maturation of the sarcomeres was characterised by a short delay in the establishment of the pattern for M-line epitopes of titin with respect to Z-disk epitopes and the incorporation of the M-line component myomesin, which preceded that of myosin binding protein-C. Thus dense body-like structures, made up of titin, (&agr;)-actinin and actin filaments serve as the first organised complexes also during myofibrillogenesis in situ and titin functions as a ruler for sarcomere assembly as soon as its C termini have become localised. We suggest that assembly of thin and thick filament occurs independently during myofibrillogenesis in situ and that myomesin might be important for integrating thick filaments with the M-line end of titin.  (+info)

Different domains of the M-band protein myomesin are involved in myosin binding and M-band targeting. (6/1432)

Myomesin is a 185-kDa protein located in the M-band of striated muscle where it interacts with myosin and titin, possibly connecting thick filaments with the third filament system. By using expression of epitope-tagged myomesin fragments in cultured cardiomyocytes and biochemical binding assays, we could demonstrate that the M-band targeting activity and the myosin-binding site are located in different domains of the molecule. An N-terminal immunoglobulin-like domain is sufficient for targeting to the M-band, but solid-phase overlay assays between individual N-terminal domains and the thick filament protein myosin revealed that the unique head domain contains the myosin-binding site. When expressed in cardiomyocytes, the head domains of rat and chicken myomesin showed species-specific differences in their incorporation pattern. The head domain of rat myomesin localized to a central area within the A-band, whereas the head domain of chicken myomesin was diffusely distributed in the cytoplasm. We therefore conclude that the head domain of myomesin binds to myosin but that this affinity is not sufficient for the restriction of the domain to the M-band in vivo. Instead, the neighboring immunoglobulin-like domain is essential for the precise incorporation of myomesin into the M-band, possibly because of interaction with a yet unknown protein of the sarcomere.  (+info)

Effect of rate of distraction on loss of range of joint movement, muscle stiffness, and intramuscular connective tissue content during surgical limb-lengthening: a study in the rabbit. (7/1432)

Surgical lengthening of limbs often results in loss of range of joint movement and this has been shown to be associated with an increase in passive tension and an increase in collagen content of the muscles. In this study, we have investigated the length/tension properties and the connective tissue component of muscle distracted at three different rates in order to determine whether low rates of distraction would enable the connective tissue component, as well as the contractile component (number of serial sarcomeres), to adapt more completely to the increased functional length of the muscle and thus lead to improved range of joint movement. It was found that loss of range of movement varied with rate of distraction. At the low rate, there was no change in the passive tension or collagen content compared to muscles from sham-operated animals, and range of movement was significantly greater than at the other rates. At the medium rate, although the muscles showed good adaptation in terms of serial sarcomere number, passive tension and collagen content was increased and range of movement reduced, indicating that changes in the connective tissue component are important factors in loss of joint movement. In the case of muscle distracted at a high rate, failure of the muscle fibres to add on sufficient sarcomeres, combined with changes in the connective tissue, resulted in almost total loss of joint movement.  (+info)

Cross bridge-dependent activation of contraction in cardiac myofibrils at low pH. (8/1432)

Striated muscle contracts in the absence of calcium at low concentrations of MgATP ([MgATP]), and this has been termed rigor activation because rigor cross bridges attach and activate adjacent actin sites. This process is well characterized in skeletal muscle but not in cardiac muscle. Rigor cross bridges are also thought to increase calcium binding to troponin C and play a synergistic role in activation. We tested the hypothesis that cross bridge-dependent activation results in an increase in contractile activity at normal and low pH values. Myofibrillar ATPase activity was measured as a function of pCa and [MgATP] at pH 7.0, and the data showed that, at pCa values of >/=5.5, there was a biphasic relationship between activity and [MgATP]. Peak activity occurred at 10-50 microM MgATP, and [MgATP] for peak activity was lower with increased pCa. The ATPase activity of rat cardiac myofibrils as a function of [MgATP] at a pCa of 9.0 was measured at several pH levels (pH 5.4-7.0). The ATPase activity as a function of [MgATP] was biphasic with a maximum at 8-10 microM MgATP. Lower pH did not result in a substantial decrease in myofibrillar ATPase activity even at pH 5.4. The extent of shortening, as measured by Z-line spacing, was greatest at 8 microM MgATP and less at both lower and higher [MgATP], and this response was observed at all pH levels. These studies suggest that the peak ATPase activity associated with low [MgATP] was coupled to sarcomere shortening. These results support the hypothesis that cross bridge-dependent activation of contraction may be responsible for contracture in the ischemic heart.  (+info)

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