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Biomedical subjects

J O Pickles

Publications and source records attributed to J O Pickles.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mechanoelectrical transduction by hair cells.

Hair cells of the inner ear are one of nature's great success stories, appearing early in vertebrate evolution and having a similar form in all vertebrate classes. They are specialized columnar epithelial cells, with an array of modified microvilli or stereocilia on their apical surface, interconnected by a series of linkages. The mechanical stimulus causes deflection of the stereocilia, stretching linkages between them, and opening the mechanotransducer channels. On a slower timescale, hair cells adapt in order to maintain optimum sensitivity, with an adaptation motor within the stereocilia acting to keep the resting tension on channels constant.

Animals↗
PubMed1991

Paired development of hair cells in neuromasts of the teleost lateral line.

Lateral line neuromasts of the bullseye Parapriacanthus ransonetti and the cardinal fish Apogon cyanosoma were examined by scanning electron microscopy. Neuromasts showed large numbers of degenerating hair cells and immature hair cells, suggesting a high degree of hair cell turnover. New hair cells were mainly produced in pairs (fewer than 5% appear singly), the two cells of a pair having opposite but parallel orientations of their mechanosensitive axes. It is suggested that each pair results, directly or indirectly, from a single mitosis. The results further suggest that the axis of mitosis is one of the factors which determine the direction of the hair cell axis of mechanosensitivity.

Animals↗
PubMed1991

Effects of streptomycin on development of the apical structures of hair cells in the chick basilar papilla.

A single dose of streptomycin (166 mg/kg egg weight) was given to chick embryos 7-15 days after the beginning of incubation. Embryos were fixed 4-12 days later, and the hair cells examined by scanning and transmission electron microscopy. The highest proportion of abnormalities was produced by injections on or before the 11th day of incubation, later injections affecting a substantially smaller proportion of embryos. This suggests the possibility of a critical period for streptomycin ototoxicity in the chick. In addition to the normal signs of cellular degeneration, the most striking abnormality was a massive expansion in the apical surface, sometimes by a factor of 20, in area. The organisation of stereocilia was also commonly affected. The stereocilia could be broken up into multiple small separate bundles, and often there was a wide separation between the kinocilium and the stereocilia. Stereocilia tended to be reduced in number, fused, and either of abnormally large, small, or irregular diameters. Structures with the appearance of stereociliar cores often lay horizontally within the surface of the cuticular plate, sometimes running for 15 microns or more. Sometimes abnormal 'stereocilia' were expressed around the extreme margins of the cuticular plate. In addition, adjacent hair cells could show very different developmental stages, as though the development of some cells had been arrested. With all these changes, the short hair cells in the centre of a papillar cross-section tended to be the most affected, with the tall hair cells and the short hair cells on the extreme inferior (i.e. abneural) edge being least affected. It is suggested that the streptomycin alters the balance of the different aspects of development of the hair cells. It might therefore be possible to use ototoxicity as a way of analysing hair-cell development.

Animals↗
PubMed1991

The development of links between stereocilia in hair cells of the chick basilar papilla.

Auditory papillae of chicks (embryonic age 6-21 days) were examined by scanning and transmission electron microscopy, in order to trace the development of the tip links between the stereocilia, and in order to trace the development of the spatial organisation of the tip links. In the most immature bundles, stereocilia were not graded in height, while strands of tenuous material interconnected adjacent stereocilia, this material being concentrated in a band near the tips of the stereocilia. The material joined the stereocilia in all directions, with no preferential direction for the interconnecting material being visible. Similarly, no columnar organisation of the stereocilia was visible. As soon as a gradation in height of the stereocilia began to appear, material could be seen running upwards from the shorter stereocilia to the adjacent lengthening stereocilia. There was a continuum in appearance between (i) the material running laterally between short immature stereocilia, (ii) the material running upwards between stereocilia which were developing a gradation in height, and (iii) the tip links seen in more mature bundles. It is suggested that tip links are a specialisation of the links which join immature stereocilia laterally near their tips. It is also suggested that the orientation of tip links, parallel to the hair cell axis of bilateral symmetry, is produced by the gradient in growth of the stereocilia.

Animals↗
PubMed1991

Morphological correlates of mechanotransduction in acousticolateral hair cells.

The development of ideas on mechanotransduction in acousticolateral hair cells is described, leading to the current idea that transduction depends on deflection of the bundle of stereocilia by a force parallel to the plane of the sensory epithelium. Electrophysiological experiments are summarised, suggesting that transduction depends on a shear between the different rows of stereocilia, and that the transducer channels are situated towards the tips of the stereocilia. Analysis of the ways that shear between the rows of stereocilia could be detected suggests that tip links are the structures which are most likely to transmit the stimulus-induced forces to the transducer channels on the membrane. The directional selectivity of mechanotransduction is associated with the position of the kinocilium and gradation in heights of the stereocilia; evidence is presented suggesting that in the lateral line these are partly determined by the mitosis giving rise to the hair cell. Tip links differentiate out of links which initially join the stereocilia in all directions, with their final spatial organisation, which sets the directional selectivity of mechanotransduction, probably being determined by the gradient in growth of the stereocilia.

Animals↗
PubMed1990

Influence of collagenase on tip links in hair cells of the chick basilar papilla.

Chick basilar papillae were incubated in collagenase, using concentrations previously employed for the isolation of viable hair cells. When assessed by scanning electron microscopy, the hair bundles had a normal conformation, with no loss of tip links compared with control incubations. The results suggest that collagenase dose not destroy the integrity of structures on the apical surface of hair cells, and that tip links are not composed of collagen. The results are in agreement with the hypothesis that tip links are involved in mechanotransduction.

Animals↗
PubMed1989

Tip-link organization in anomalously-oriented hair cells of the guinea pig cochlea.

Stereocilia are described in a group of guinea pigs with abnormal conformation of the outer hair cell stereociliary bundles. Rows of stereocilia were found which were circular instead of V- or W-shaped, and rotated or even reversed in orientation with respect to normal. The stereocilia have however a normal gradation in heights of the rows of stereocilia, and have tip links running in the direction of gradation in height.

Animals↗
PubMed1989

The organization of tip links and stereocilia on hair cells of bird and lizard basilar papillae.

Auditory papillae from three species of bird (pigeon, starling, and chick), and two species of European lizard (Podarcis muralis and Podarcis sicula) were examined by scanning electron microscopy. Hair bundles from all papillae showed tip links oriented along the direction of gradation in heights of the stereocilia (i.e. parallel to the hair-cell axis of bilateral symmetry, and so parallel to the excitatory-inhibitory axis for mechanotransduction). This orientation was seen irrespective of the overall orientation of the hair bundle within the papilla. The stereocilia formed columns, joined by the tip links, which ran parallel to the hair-cell axis of bilateral symmetry. The stereocilia within the same column tended to stay together, while those in different columns tended to separate during preparation. In many columns all the stereocilia tended to be a little taller, or a little shorter, than the equivalent stereocilia in adjacent columns, suggesting that all the stereocilia within one column had been affected by a common height determinant during development. In addition, links running laterally between stereocilia were seen, in a band near the base of the stereocilia. The results are consistent with the hypothesis that tip links are a universal feature of mechano-transducing acousticolateral hair cells, and that they are involved in sensory transduction. The results also support suggestions that the tip links may play a role in determining the heights of the stereocilia during development.

Animals↗
PubMed1988

Further observations on the fine structure of tip links between stereocilia of the guinea pig cochlea.

Stereocilia of the guinea pig organ of Corti were examined by transmission electron microscopy, after fixation in glutaraldehyde and tannic acid, and postfixation and en bloc staining in osmium tetroxide, tannic acid, uranyl acetate, and phosphotungstic acid. Tip links were observed between the stereocilia. The links emerged from the tips of the shorter stereocilia in the hair bundle, running nearly at right angles to the cuticular plate, to join the side-wall of the adjacent taller stereocilium of the next row. The tip links had a fine filamentous core, approximately 6 nm in diameter. The core was surrounded by positively-staining amorphous material, which had a variable appearance from link to link. The central filament inserted into membrane specialisations at both its upper and lower ends. The results suggest that tip links have two components, and that the central filament, which has the same diameter as an actin filament, is suitable for transmitting stimulus-induced movements to the transducer channels of the stereocilium. The central filament would therefore concentrate the stimulus-induced forces onto a small area of cell membrane.

Animals↗
PubMed1987

Vulnerability of tip links between stereocilia to acoustic trauma in the guinea pig.

The cochleae of anaesthetized guinea pigs were prepared for scanning electron microscopy, immediately after exposure to an intense tone. Stereocilia on hair cells showing relatively small degrees of disruption were analyzed. If the bundles of stereocilia showed no or only a very slight degree of disorganization, the fine links emerging from the tips of the shorter stereocilia remained intact. If the stereocilia were separated more than a very little, the tip links between stereocilia were no longer visible. However, it was possible for tip links to remain intact in some parts of the hair bundle, while tip links in other, more disrupted parts, were lost. In outer hair cells, tip links did not seem any more vulnerable in one position than in another. In inner hair cells, it was commonly found that the tip links running between the tallest stereocilia and the next row of shorter stereocilia had broken, while the tip links running between the other shorter rows of stereocilia remained intact. The results suggest that tip links between stereocilia are preserved as long as the other links between the stereocilia and the cytoskeleton of the stereocilium remain intact. When the latter are damaged the tip links fracture. The results also suggest that, if the tip links are indeed involved in transduction, some degree of stimulus transduction can continue in damaged inner hair cells, albeit with a reduced sensitivity.

Acoustic Stimulation↗
PubMed1987

The effect of chronic application of kanamycin on stereocilia and their tip links in hair cells of the guinea pig cochlea.

Albino guinea pigs were treated with kanamycin (400 mg/kg i.p.) daily for 10 days. After a 2-week recovery period their cochleae were analyzed by scanning electron microscopy. Attention was paid to those outer hair cells which had been less severely damaged. Stereocilia of the outer hair cells were often constricted at the root, and in some cases had become detached at the root. In stereocilia showing any degree of abnormality, the tip links were usually missing. However, in a few exceptional cases, tip links could remain on stereocilia showing other abnormalities, such as constriction at the root. Where hair cells were otherwise apparently unaffected, a much higher proportion of tip links remained, even on cells situated in an area of extensive hair cell loss. The results give further information on the process of kanamycin poisoning. They also suggest that substantial loss of tip links, and therefore perhaps of transduction, is one of the preliminary consequences of kanamycin poisoning.

Animals↗
PubMed1986

Crosslinks between stereocilia in hair cells of the human and guinea pig vestibular labyrinth.

The saccules and ampullae of the semicircular canals from human and guinea pig temporal bones were fixed in glutaraldehyde without osmium. Crosslinks were seen between stereocilia of the vestibular hair cells, similar to those previously demonstrated in the guinea pig, although an additional set of crosslinks was displayed: first, horizontal crosslinks were seen between adjacent stereocilia, occupying most of the length of the hair bundle; secondly, a single upward-pointing link ran from the apex of each shorter stereocilium into the shaft of the adjacent taller stereocilium; thirdly, an extensive array of horizontal links were demonstrated between stereocilia close to their insertion into the cuticular plate. We suggest that these basal crosslinks support the long vestibular stereocilia rendering them more rigid, and that the upwind pointing crosslinks are responsible for the initiation of sensory transduction.

Aged↗
PubMed1986

Early morphological and chemical changes induced by cisplatin in the guinea pig organ of Corti.

Guinea pigs were treated with a single dose of Cisplatin (5 mg IP). After 2-4 days the cochleas were prepared for morphological analysis by scanning electron microscopy and chemical analysis by X-ray dispersive microanalysis. Following Cisplatin, the bundles of stereocilia on the hair cells were found to be rough, disarrayed, fused, and finally absorbed. Significant increases were found in the levels of calcium, sulphur, and phosphorus in the abnormal hair cells. It is suggested that the high calcium levels might be due to the inhibition of enzymes which normally keep cytoplasmic calcium low, and that some of the changes in the stereocilia might be secondary to this.

Animals↗
PubMed1985

Osmium tetroxide postfixation in relation to the crosslinkage and spatial organization of stereocilia in the guinea-pig cochlea.

Guinea-pig cochleae were fixed in glutaraldehyde, followed by short (30 s), intermediate (3 min) or long (24 h) periods of postfixation in 1% osmium tetroxide. The hair cells of the organ of Corti were examined by scanning electron microscopy. Following short periods of postfixation in osmium tetroxide, the preservation of crosslinks between the stereocilia could be enhanced, compared to the picture seen without postfixation. Moreover, in many cases the stereocilia parted slightly, revealing many lateral links between the stereocilia, which were otherwise hidden. The tip of each shorter stereocilium on a hair cell gave rise to a single, vertically pointing link, which ran upwards to the taller stereocilium of the adjacent row on the hair cell. It is suggested that distortion of such links is associated with sensory transduction. An extensive array of lateral links, connecting the stereocilia of the same and different rows on the hair cell, was also seen. In addition, the surface membranes of the stereocilia had a granular appearance. Following intermediate and long periods of postfixation in osmium tetroxide, crosslinks were rarely seen, and the stereocilia had smooth or wavy rather than granular surface membranes. Moreover, the spatial organization of the stereocilia, particularly on inner hair cells, was disrupted. In tissue postfixed for short periods, it was possible to map the directions of the vertically pointing links, and see the three-dimensional arrangement of the stereocilia. It was shown that the V-shape of the rows of stereocilia on outer hair cells, and the straight-line arrangement of the stereocilia on inner hair cells, were both appropriate for a maximal sensitivity of the hair cells to deflection of their stereocilia in a radial direction. It is suggested that the differences in the shape of the rows on inner and outer hair cells are derived from the different packing of the stereocilia on the two types of hair cell.

Animals↗
PubMed1985

Cross-links between stereocilia in the human organ of Corti.

Human cochleae were fixed in glutaraldehyde, without the use of osmium. Cross-links were seen between the stereocilia, similar to those we have previously reported for the guinea pig: first, stereocilia of the same row on each hair cell were joined by horizontally-running links; secondly, the shorter stereocilia had pointed tips, each giving rise to a single, vertically-pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link is involved in sensory transduction. The links were sparser than had been seen in the guinea pig which may be a reflection of the vulnerability of the links to non-optimal fixation, and the greater difficulty in producing good fixation in human specimens.

Adult↗
PubMed1984

Morphology and cross-linkage of stereocilia in the guinea-pig labyrinth examined without the use of osmium as a fixative.

Hair cells of the guinea-pig cochlea and vestibular system were prepared for electron-microscopic examination by fixing in glutaraldehyde without the use of osmium. An extensive array of cross-links was seen between the apical ends of the stereocilia, by both scanning and transmission electron microscopy. Some cross-links ran laterally between stereocilia of the same row. Others ran laterally between the stereocilia of the different rows, holding the tips of the shorter stereocilia in towards the longer stereocilia of the next row. In addition, each tip on the shorter stereocilia gave rise to a single, upwards pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link might be involved in the mechanics or even the membrane biophysics of sensory transduction. With this method of preservation, all the apical surface membranes of the hair cells appeared rough, and contained dense granules. The roughness was greatest in the parts of the stereocilia to which the cross-links were attached. The mitochondrial and synaptic membranes of the hair cells appeared normal.

Animals↗