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J Davidowitz

Publications and source records attributed to J Davidowitz.

At least 19 recordsLinked to original sources

Location along the muscle's length is a determinant of myofibril size.

In a previous study of myofibril size in 'Pale' (fast-twitch-glycolytic) fibers of rabbit extraocular muscle (EOM), it was found that individual long Pale fibers demonstrate a substantial increase in the size of myofibril profiles from their proximal to their distal halves (Davidowitz et al., 1996b). That finding raised the question of whether such proximal-to-distal increase of myofibril size in the Pale fibers is determined by: (1) longitudinal position within the individual muscle fibers themselves or (2) location along the length of the muscle as a whole? This question was tested in the present study by comparing the original group of long Pale fibers, which extend the full length of the muscle, with two groups of short Pale fibers, which are respectively confined to the proximal and distal halves of the muscle. It was found that (a) in the proximal half of the muscle, the short fibers and the adjacent portions of the long fibers have the same smaller size of myofibrils, and (b) in the distal half of the muscle, the short fibers and the adjacent portions of the long fibers have the same larger size of myofibrils. This finding indicates that the proximal-to-distal increase of myofibril-profile size in these EOM Pale fibers is determined by location along the length of the muscle as a whole, and is not related to longitudinal position within the individual fibers themselves.

Animals↗

Myofibril size variation along the length of extraocular muscle in rabbit and rat. I: orbital layer.

It is generally assumed that a muscle fiber is structurally uniform along its length. That assumption is not consistent with the observed variation of myofibrillar profile size along the length of both singly innervated fibers (SIFs) and multiply innervated fibers (MIFs) in the orbital (outer) layer of extraocular muscle (EOM). Muscle fibers were reconstructed in serial sections along the orbital layer of rabbit and rat EOM. For both the SIFs and MIFs, myofibril profile size was smallest (narrowest) near the endplate. In the SIFs of rat, for example, the myofibril profiles were 28% wider at a distance of 1.5 mm from the endplate than at the endplate itself. Measures of profile size included the mean intercept length and the mean shortest path from test points within the profile to the profile boundary. The possible effect of sarcomere length variation was controlled by normalizing the myofibrillar profile size data to a constant spacing of the myosin filament lattice. This morphometric approach was also used to quantify the further increase of profile size that occurs in the end portions of the orbital MIFs where the myobrillar organization is typically ill-defined.

Animals↗

Myofibril size variation along the length of extraocular muscle in rabbit and rat. II: global layer.

Systematic variation of myofibril profile size was observed along the length of both singly innervated fibers (SIFs) and multiply innervated fibers (MIFs) of the global (inner) layer of extraocular muscle (EOM). These findings contrast with the assumption that global layer fibers of EOM are structurally uniform along their length. Muscle fibers were reconstructed in serial sections along the global layer of rabbit and rat EOM. Long fibers of the 'Pale' SIF (fast twitch glycolytic) and the MIF (tonic) populations were sampled by EM in both proximal and distal portions of the muscle. In rabbit, myofibril size of the Pale SIFs showed a proximal-to-distal increase of 28% whereas the MIFs showed a proximal-to-distal decrease of 10%. In rat, these two fiber populations showed analogous smaller changes. Measures of profile size included the mean intercept length and the mean shortest path from test points within the profile to the profile boundary. The possible effect of sarcomere length variation was controlled by normalizing the measures to a constant spacing of the myosin filament lattice.

Animals↗

Expression of a novel combination of fast and slow troponin T isoforms in rabbit extraocular muscles.

The properties of extraocular muscles (EOMs) are quite different from those of the trunk and limb. Here we show that there is a novel pattern of troponin T (TnT) expression in EOMs which most likely contributes to the fine control of ocular movement and may reflect their innervation by cranial motoneurons. Three regions of the muscle were analysed to distinguish the TnT isoforms present in the fast singly-innervated fibres from those in the multiply-innervated fibres. More than 95% of the TnT in the singly-innervated fibres is TnT3f, which exhibits the most graded response to changes in calcium concentration during activation (Schachat et al., J. molec. Biol. 198, 551-4). In multiply-innervated fibres, which exhibit tonic contractures, the slow troponin T TnT2s is expressed. While neither TnT3f nor TnT2s is unique to EOM, this pattern is unusual in two respects: first, both TnT3f and TnT2s are minor components of the trunk and limb musculature, and second, most muscles express several fast and both slow TnT species. Although EOM occupies a highly specialized physiological niche, its unusual physiology is not reflected in the presence of new TnT isoforms but in the expression of a different ratio of the known species of TnT.

Animals↗

Cadmium reduces extraocular muscle contractility in vitro and in vivo.

Cadmium, a blocker of calcium channels in various excitable cells, reduces the contractility of extraocular muscles. When applied to rat extraocular muscles in vitro, it reduces the sustained or tonic tension generated by the tonic multiply innervated fibers of the global layer of the muscles. When injected in vivo into rabbit extraocular muscles, it produces a temporary paralysis of the muscles and a deviation of the eye position. These effects are presumed to involve a blockade of the calcium channels of the muscle fibers and of the neuromuscular junctions. It is proposed that, on the basis of these effects, a non-surgical treatment of strabismus could be developed.

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Intermitochondrial junctions in the extraocular muscle of the rat.

Intermitochondrial junctions with a spacing of 17-21 nm were observed in the superior rectus muscle of a rat. Periodic rounded densities are aligned midway between the apposed outer mitochondrial membranes at some of these junctions. Such densities have a diameter of about 8-10 nm and a center-to-center spacing of about 26-30 nm. These junctions occur in cases where one mitochondrial profile is enclosed within another or where two profiles are interlocked so that their combined overall form has a smoothly contoured profile. Intermitochondrial junctions seem not to have been previously described in muscle, but have been reported in other kinds of tissues. In agreement with those previous reports, the presently observed intermitochondrial junctions usually involve mitochondria that display atypical features indicative of tissue abnormality or stress. Such junctions were never observed in normal extraocular muscle.

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Distribution of mitochondrial and lipidic alterations in abnormal extraocular muscle of rat.

An abnormal superior rectus muscle of rat displayed marked differences in the respective distributions of mitochondrial alterations and excessive lipid accumulations, both of which are thought to be indicators of faulty oxidative metabolism. The mitochondrial alterations were widespread, extending over 46% of muscle length. In contrast, the excess lipids extended over but 11% of the muscle length and were virtually confined to the end-plate region. The end plates themselves were essentially normal. These data raise the possibility that the end-plate region may exhibit a locally greater deficit of oxidative metabolism, due to a possibly higher metabolic requirement needed to support the localized end-plate potential activity.

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Latter reorganization of membrane-glycogen complexes in rabbit extraocular muscle.

Characteristic modes of secondary reorganization were observed in membrane-glycogen complexes of rabbit extraocular muscle. These included (a) an irregular widening or narrowing of the intracisternal space, (b) a loss of the typical intracisternal flocculent densities, and (c) the acquisition of intercisternal flocculent densities. In irregularly widened cisternae, the membranes tended to remain closely adjacent to the intervening glycogen layer, thereby forming triads composed of a glycogen layer enclosed within the apposing membranes of adjacent cisternae. In the absence of glycogen particles from contiguous portions of several lamellae, the membranes became compacted to form myeloidlike figures. Degenerating complexes sometimes displayed distention of intercisternal spaces and layers of atypically small particles. The above modifications of membrane-glycogen complexes would be compatible with the notion that these structures are involved in the process of glycogen metabolism, as opposed to the previously suggested notion that these structures are transient vehicles for the accumulation of glycogen masses.

Animals↗

Membrane-glycogen complexes in rabbit extraocular muscle.

Analysis of 432 electron micrographs of membrane-glycogen complexes revealed that: (1) Golgi apparatus is closely associated with 4.2% of the complexes, such associations occurring irrespective of the degree of glycogen loading in the complex. (2) Apparent ribosomes are seen in association with about 30% of the complexes, either attached to membranes or enclosed between cisternae. (3) In longitudinal sections of the muscle fibers, complexes may form columns which extend for as much as 40 microns along the fiber. (4) Various cytoplasmic organelles may become enclosed within a complex. (5) Some cisternae of a complex may assume the form of randomly oriented tubules, in contrast to the typical systematic array of flattened cisternae. (6) Some cisternae of a complex may become distended in a wide and uneven manner, in contrast to the typical narrow and even distension.

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Cytoplasmic inclusions in rabbit extraocular muscle.

Cytoplasmic inclusion bodies, similar to those previously described in abnormal and normal human extraocular muscle, were observed in the orbital surface layer of the superior rectus muscle in rabbit. These inclusion bodies are composed of a flocculent material of low density studded with granular foci of increased density. In sequential samples of serially reconstructed muscle fibers visualized by electron microscopy, cytoplasmic inclusion bodies were seen in 4.5% of 1187 samples through multiply innervated fibers that vary systematically in diameter along their length; inclusion bodies were also seen in 0.8% of 354 samples through multiple innervated fibers of constant diameter. Cytoplasmic inclusion bodies were not seen in 1838 samples through singly innervated fibers. These data suggest that such inclusion bodies may occur preferentially in multiply innervated fibers. The present findings are not compatible with previous suggestions that such cytoplasmic inclusion bodies may be indicative of a pathologic or aging process. These findings are consistent with previous suggestions that such inclusion bodies are to be considered as normal structures in extraocular muscle.

Animals↗

Variation of mitochondrial volume fraction along multiply innervated fibers in rabbit extraocular muscle.

Mitochondrial volume fraction was compared among three regions along the length of six multiply innervated fibers (MIFs) in the orbital surface layer of rabbit superior rectus. These MIFs are of about 5 micrometer diameter toward the middle of their length, and of about 15 micrometer diameter toward their proximal and distal ends. The region of highest volume fraction (26%) was located toward the proximal end of their segment of minimal diameter, in apparent association with endplate-like nerve junctions. The region of lowest volume fraction (8%) was located at their distal segment of maximal diameter. The region toward the distal end of their segment of minimal diameter displayed an intermediate volume fraction (15%). These mitochondrial volume fractions were further analyzed in terms of the relative contributions of the I-band, the A-band, and the subsarcolemmal mitochondrial clusters. Comparable changes in mitochondrial content occur in both the I-band and A-band; in the fibers' distal segment of maximal diameter, however, the mitochondrial volume fraction in the A-band (5%) is lower than in the I-band (11%). These modifications of mitochondrial content along the fibers' length occur irrespective of the contributions of the subsarcolemmal mitochondrial clusters.

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The distribution of membrane-glycogen complexes in the orbital surface layer of rabbit superior rectus.

The distribution of membrane--glycogen complexes along the length of individual muscle fibers was compared among three fiber populations in the orbital surface layer of rabbit superior rectus. These three populations were (a) 61 singly innervated fibers (SIFs), (b) 10 multiply innervated fibers of relatively constant 10 micrometer diameter (10 micrometer MIFs), and (c) 22 multiply innervated fibers which are of about 5 micrometer diameter toward the middle of their length and of about 15 micrometer diameter toward their proximal and distal segments (5--15 micrometer MIFs). The orbital surface layer was sampled by electron microscopy at 68 sequential locations. Membrane--glycogen complexes were not seen in any of the 1738 samples of the SIFs. In the MIFs, such complexes were observed in 14% of the 1541 samples. However, both the 10 micrometer MIFs and 5--15 micrometer MIFs displayed a preferential concentration of membrane--glycogen complexes toward their distal fiber portions, and such complexes were seen in about 50% of the MIF samples near the beginning of the muscle's distal third. In the distal portion of 5--15 micrometer MIFs, there was a direct relationship between their increasing fiber diameter and their increasing frequency of occurrence of membrane--glycogen complexes.

Animals↗

Light and electron microscopic serial analysis of mouse extraocular muscle: morphology, innervation and topographical organization of component fiber populations.

Mouse superior rectus extraocular muscle was examined in serial section by light and electron microscopy. By such analysis, it was possible to discriminate single versus multiple innervation, characteristics of internal cell morphology, and topographical distribution of the respective fiber populations within the muscle. Singly innervated (SIF) and multiply innervated fibers (MIF) were observed, both in an orbital surface layer and in the underlying global region of the muscle. Five morphologically distinct fiber types (three SIF and two MIF) were discriminable in terms of fiber diameter, mitochondrial richness, development of the sarcoplasmic reticulum, and myofibrillar size. Many fibers both SIF and MIF, terminated variously along the length of the muscle. The diameter of orbital MIF typically varied from one end of the fiber to the other by a factor of about three; the global MIF were of essentially constant diameter. The junctional complexity varied among the respective types of SIF. The MIF of both the global and orbital regions exhibited comparable ranges of complexity in their neuromuscular junctions.

Animals↗

Congenital total external ophthalmoplegia associated with infantile spinal muscular atrophy. Fine structure of extraocular muscle.

A case of total congenital external ophthalmoplegia associated with infantile spinal muscular atrophy is presented. In the first 29 months of life, ophthalmoplegia has remained complete. Ultrastructure of lateral rectus extraocular muscle indicates a neurogenic process as the basis of the ophthalmoplegia. Light microscopy alone is insufficient to distinguish primary "myopathic" from "neurogenic" disease in external eye muscles.

Child, Preschool↗