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Biomedical subjects

M S Forbes

Publications and source records attributed to M S Forbes.

At least 37 records · Page 2Linked to original sources

Association between mitochondria and gap junctions in mammalian myocardial cells.

In ventricular myocardial cells of mouse, guinea-pig, dog, and monkey, mitochondria frequently form close associations with gap junctions, the two structures being separated by a space of 20 nm or less. Similar appositions are found in both the mature atria and the developing myocardium of the mouse. The gap junctions assume a variety of configurations with respect to the apposed mitochondria. These include profiles in which the gap junctions conform closely to the contours of mitochondria, as well as profiles in which finger-like sarcolemmal evaginations, composed entirely of gap junctions, extend longitudinally or transversely into an adjoining cell to envelop mitochondria. In mouse ventricular wall, over 40% of the length of gap junctions is juxtaposed to mitochondria and strands of connecting material are often present in the interspace between the two structures. In addition, in freeze-fracture replicas, portions of mitochondria are found attached to areas of myocardial sarcolemma that contain gap-junction particles. Since mitochondria are known to sequester Ca2+ ion, it is possible that the close association between mitochondria and gap junction may function to buffer the intracellular Ca2+ concentration near the gap junctions, and thereby regulate the the ionic permeability of the gap junctions.

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Electron-microscopic studies on reaggregate cultures of vascular smooth muscle cells from normotensive and spontaneously hypertensive rats.

Vascular smooth muscle cells were taken from the aortae of the WKY (normotensive) and SHR (spontaneously hypertensive) strains of rat by enzymatic dispersion and put into reaggregate culture. Initially the cells became individual spheroids having average diameters of 10 micrometers and surfaces that were either rough or smooth. The cells were far more complex than they appeared on their surfaces; after one day in culture, there was considerable internal variation in these cells. All the cells, whether WKY or SHR, lost the bulk of their cytoplasmic contents (including myofilaments, many mitochondria, and vesicular structures) in the early stages of culture and eventually became flattened. After 14 days in culture, these modified cells collected to form reaggregates that were commonly roughly spherical and several hundred micrometers in diameter. These reaggregates consisted of peripheral regions made up of several layers of flattened cells overlying cores formed by glia-like networks of cells similar in cytological appearance to the cells at the periphery. The meshes formed in this way contained cellular debris derived from dead cells or extrusion of cellular contents. It appears that SHR cells are quicker to form reaggregates than are WKY cells. Yet the SHR cells retained a rounded conformation after five days, whereas the WKY cells were more flattened and formed a more discrete aggregate at this stage of culture. However, by the fourteenth day of culture, differences between the two cell strains were not so pronounced, as far as could be judged by observations made with scanning and transmission electron microscopy. Both WKY and SHR cells at 14 days appeared highly secretory, possessing large Golgi systems as well as numerous ER cisternae and mitochondria. SHR cells produced greater amounts of connective tissue at all stages of culture than did WKY cells, indicating that a similar difference may contribute to the hypertension which develops naturally in situ in SHR animals.

Animals↗

Hyperpigmented patches in the skin of the newt Notophthalmus viridescens.

In the integument of the red-spotted newt there occasionally appear patches of skin which are at the same time melanistic and iridescent. Such hyperpigmented patches have been found on the back, on the tail and on the dorsal surface of both fore and hind limbs. Cytological examination of several such areas revealed the presence of large numbers of chromatophores distributed throughout the dermis. The majority of the chromatophores consisted of atypically large and dendritic melanophores, which contained typical pigment granules. The iridescence resulted from a high incidence of iridophores. Xanthophores also were found in considerable abundance. This extensive and apparently random intermingling of melanophores, iridophores and xanthophores in limited areas constitutes a striking exception to the usual distributional patterns of pigment cells in this animal.

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Structures located at the levels of the Z bands in mouse ventricular myocardial cells.

Within ventricular myocardial cells of the mouse, the myoplasmic regions located immediately adjacent to the Z lines of the sarcomeres contain a variety of structures. These include: (1) transversely oriented 10 nm ('intermediate') filaments that apparently contribute to the cytoskeleton of the myocardial cell; (2) the majority of the transverse elements of the T-axial tubular system; (3) specialized segments of the sarcoplasmic reticulum (SR) that are closely apposed to the sarcolemma or T-axial tubules (junctional SR); (4) 'extended junctional SR' ('corbular SR') that exists free of association with the cell membrane; (5) 'Z tubules' of SR that are intimately apposed to the Z line substance; and (6) leptofibrils. In addition, fasciae adherentes supplant Z lines where myofibrils insert into the transverse borders (intercalated discs) of the cells. The concentration of these myocardial components at the level of the Z lines suggests that a particular specialization of structural and physiological activities exists in the Z-level regions of the myoplasm. In particular, it appears that the combination of intermediate filaments, T tubules, and Z-level SR elements forms a series of parallel planar bodies that extend across each myocardial cell to impart transverse rigidity. The movement and compartmentation of calcium ion (Ca2+) would seem especially active near the Z lines of the myofibrils, in view of the preferential location there of Ca2+-sequestering myocardial structures such as T tubules, junctional SR, extended junctional SR and Z tubules.

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Ruthenium-red staining of skeletal and cardiac muscles.

The effects of ruthenium red (RR) on amphibian and mammalian skeletal muscles and mammalian myocardium were examined. In skeletal muscle cells, a discrete pattern of staining can be brought about within the lumina of the terminal cisternae (junctional sarcoplasmic reticulum [SR]) by sequential exposure to RR and OSO4. After prolonged immersion in RR solution, formation of pentalaminar segments ("zippering") occurs at various points along the longitudinal ("network") SR tubules. Zippering can be elicited in skeletal SR at any stage of preparation prior to postfixation with OSO4. By means of dispersive X-ray analysis, both ruthenium and osmium were seen to be deposited in skeletal muscle junctional SR, and ruthenium was detected in the myoplasm as well. In skeletal muscles whose T tubules were ruptured by exposure to glycerol, the pattern of SR staining and zippering resulting from ruthenium-osmium treatment was not affected. These findings indicate that RR is capable of passage across the sarcolemma of skeletal muscle and that this passage does not occur solely under conditions in which the plasma membrane is damaged. In contrast, RR does not opacify or modify any region of the SR of cardiac muscle. However, after this treatment, randomly distributed opaque bodies, composed of parallel lamellar structures, appear throughout the myocardial cells. A few of these bodies are associated with lipid droplets, but the rest are of unknown origin. The failure of the SR of cardiac muscle to stain after exposure to ruthenium dye (even though this material enters these cells) suggests that the chemical composition of cardiac SR is significantly different from that of skeletal muscle SR.

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Focal laminate segments in cytoplasmic processes of mouse myocardial fibroblasts.

In mouse ventricular myocardium, we have found unusual fibroblasts whose cellular processes in some regions are particularly flattened and which contain linearly-arranged, electron-opaque structures ('central laminae"). The morphology of these focal laminate segments of fibroblast processes suggests that the intracellular laminae are adhesive entities which hold the plasmalemmata above and below them in close parallel apposition for short distances.

Animals↗

Ultrastructure of pericytes in mouse heart.

The pericytes of mouse myocardium are extensively branched cells that form an incomplete layer around the endothelium of capillaries and postcapillary venules. The membranes of pericytes and endothelial cells are connected by specialized junctions. Microtubules, intermediate (10-nm) filaments and microfilaments are oriented within circumferentially-arranged cytoplasmic processes of pericytes so as partially to encircle the endothelial cylinder. The intracellular organization of these myocardial pericytes suggests that they are smooth muscle-like cells which may be capable of influencing microvascular dynamics in the heart.

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Innervation of myocardial microcirculation; terminal autonomic axons associated with capillaries and postcapillary venules in mouse heart.

Efferent terminal axons are associated with numerous capillaries and postcapillary venules in both the atria and ventricles of mouse heart. These axons possess ultrastructural characteristics which are typical of peripheral autonomic fibers in other tissues. Many are found near pericytes, in a relationship closely resembling that between terminal axons and smooth muscle cells of larger vessels. To demonstrate adrenergic terminals, mice were pretreated with 5- or 6-hydroxydopamine; examination of these animals' hearts revealed that both adrenergic and cholinergic axons terminate near pericytes and endothelial cells. The results of this study are consistent with the view that there may be a functional innervation of capillaries and postcapillary venules of the mouse heart.

Adrenergic Fibers↗

The presence of transverse and axial tubules in the ventricular myocardium of embryonic and neonatal guinea pigs.

Developing transverse (T) tubules are found in embryonic guinea pig ventricular myocardium after approximately eight weeks of gestation. By the time of birth (nine weeks total gestation); longitudinally-oriented axial tubules connected to the T tubules also have formed, and the majority of cells closely resemble those of the adult. The form taken by the developing T and axial tubules suggests that they are generated in a manner similar to that for T tubules in chick and rat skeletal muscle, namely by repeated formation of caveolae.

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