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S D Comis

Publications and source records attributed to S D Comis.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Cross-links between stereocilia in the guinea pig organ of Corti, and their possible relation to sensory transduction.

Hair cells of the guinea pig cochlea were preserved for electron microscopic examination by fixing in glutaraldehyde without the use of osmium. An extensive array of cross-links was seen between the stereocilia, by both scanning and transmission electron microscopy. The stereocilia were linked together laterally, particularly near their apical ends, by links running approximately at right angles to the long axis of the stereocilia. One set joined stereocilia of the same row, and another set joined stereocilia of the different rows, holding the tips of the shorter stereocilia in towards the longer stereocilia of the next row. In addition, the tip of each shorter stereocilium on the hair cell gave rise to a single, upwards-pointing link, which ran up to join the taller stereocilium of the next row. We suggest that distortion of this link would give rise to sensory transduction. On this basis, we are able to explain the V shape of the rows of stereocilia on outer hair cells. Within the rows, the three-dimensional arrangement of the stereocilia was different from that seen conventionally. Rather than standing parallel, the stereocilia of the different rows tapered in together at the tips, presumably held by the laterally-running cross-links. In addition, a membrane roughness, particularly pronounced in the region of the stereocilium which gives rise to the cross-links, was seen. However, the lateral and basal surface membranes of the hair cell, and the membranes of the internal organelles, had a more conventional appearance.

Animals↗

Chronic effects of loop diuretics on the guinea-pig cochlea.

Groups of pigmented guinea pigs (weighing 480 to 650 g at the start of the experiment) were given daily intraperitoneal injections of 16 mg/kg bumetanide or 10, 20 or 40 mg/kg furosemide over a period of 4 weeks. Two weeks following the last diuretic dose the animals were anaesthetized with urethane and the responses of single auditory nerve fibres to pure-tone and click stimuli were recorded. The tuning of individual units, as measured by Q10 dB values of frequency threshold curves, tended to be more affected than threshold at characteristic frequency by both loop diuretics. Light microscope examination of treated cochleas suggested greater effect of the drugs on the organ of Corti than on stria vascularis.

Animals↗

Threshold sensitivity of the auditory pathway: effects of worsening signal-to-noise ratio in the auditory nerve.

Perfusions of scala tympani with high potassium solutions increase spontaneous activity of auditory nerve fibres without affecting their threshold sensitivity. In these circumstances, however, the signal-to-noise ratio of the auditory nerve response to a given stimuli is worsened. Recordings from cochlear nucleus neurones during such perfusions indicate that this worsening is critical for threshold sensitivity at higher levels in the auditory pathway.

Acoustic Stimulation↗

The effects of frusemide, bumetanide and piretanide on the quinea pig cochlea and auditory nerve.

Frusemide, bumetanide and piretanide were introduced into scala tympani of the guinea pig cochlea by perfusion. The short-term effects of these drugs on the cochlear microphonic, the compound action potential and on the activity of single auditory nerve fibres were studied. the compound action potential was more sensitive to the action of the above compounds than was the cochlear microphonic. Single auditory nerve fibres showed a marked increase in threshold and generally a fall in spontaneous firing rate. A deterioration in in tuning was observed which in some cases, was not invariably accompanied by a rise in threshold. Histological examination revealed oedematous changes in stria vascularis and in supporting cells following cochlea perfusion with the above compounds.

Animals↗

Is myosin in the cochlea a basis for active motility?

Recent evidence suggests that the stereocilia of cochlear hair cells contain actin filaments. The experiments reported here demonstrate the presence of myosin, suggesting that the mechanical properties of the hair cells may be actively modifiable by actin-myosin interactions as in muscle cells.

Actins↗

Kanamycin ototoxicity and pigmentation in the guinea pig.

Cochleas from albino and pigmented guinea pigs were examined histologically following chronic administration of Kanamycin. In pigmented animals, damage was concentrated amongst hair cells towards the base, but in albinos, hair cell damage was diffusely spread. These observations support suggestions that melanin is implicated in Kanamycin ototoxicity.

Animals↗

Effects of increased potassium in scala tympani on auditory nerve sensitivity.

Raising the K+ concentration in scala tympani of the guinea-pig cochlea generally caused a substantial increase in the spontaneous firing rate of single auditory nerve fibres. This effect was not accompanied by any observed reduction in the threshold sensitivity of these fibres. These findings cast doubt on current theories of cochlear transduction.

Action Potentials↗

Action of putative neurotransmitters in the guinea pig cochlea.

Scala tympani of the guinea pig was perfused with artificial perilymph containing putative transmitter substances. Single auditory nerve fibre activity was recorded during these perfusions and the responses of these fibres were studied using computer-controlled routine. Acetylcholine significantly inhibited tone-induced responses of a large proportion of the fibres tested. Glutamate appeared to be a potent depolarising agent when applied in concentrations between 2 and 10 mM. Noradrenaline did not affect tone-induced activity, but inhibited the spontaneous activity of some fibres. The results support the view that acetylcholine is the transmitter at synapses of the olivocochlear bundle, and that glutamate may be involved in the afferent synapse. The data do not support the hypothesis that noradrenaline is the afferent transmitter.

Acetylcholine↗

Relationship of centrifugal fibres to 'supporting' cells.

We have described cholinergic fibres which cross the tunnel to three levels of the cells on the opposite side--from the level of the efferent network to the base of a plaque at the level of the nucleus of the first Deiters cell. These fibres are dependent upon the OCB being intact. The same is true for those fibres seen within the Hensen cell region. However, the cholinesterase-staining fine fibres travelling along the floor of the tunnel to the base of the plaque are independent of the integrity of the OCB.

Acetylcholinesterase↗