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PubMedDate not supplied

Active nonlinear mechanics of the organ of Corti including the stereocilia-tectorial membrane complex.

There is a large amount of knowledge about the different components of the organ of Corti (OC), but little is known about how these components act together in vivo. To clarify the complex mechanical behavior of the OC, anatomic results are carefully analyzed and used to develop a finite element model of a short section of OC, which includes 8 outer hair cells (OHC) and their supporting structures. The modal analysis shows the frequency-dependent phase reversal of the radial stereocilia displacement. The transient computation confirms the amplification of OC displacements when the ability of the OHC to contract and elongate is considered. The inclusion of a nonlinear function describing the mechanoelectrical transduction in OHC amplifies and distorts the displacement of the OC when it is stimulated by a sinusoidal input pressure function. These results are in agreement with other psychoacoustic, electrophysiologic and otoacoustic measurements.

Biomechanical Phenomena↗

PubMed1989

CGRP-like immunoreactivity in the guinea pig organ of Corti: a light and electron microscopy study.

We examined calcitonin-gene related peptide (CGRP)-like immunoreactivity in the guinea pig organ of Corti at both the light and electron microscope level using immunofluorescence and immunoperoxidase techniques. We observed strong CGRP-like immunoreactivity in the inner spiral bundle and tunnel spiral bundle in all turns at both the light and electron microscope level. CGRP immunostaining was localized exclusively in vesiculated efferent fibers. The majority of these fibers in the inner spiral bundle were immunoreactive. We observed immunostained synaptic junctions between two efferent fibers and between efferent varicosities and afferent dendrites. In the region of the outer hair cells (OHC), we found CGRP-like immunoreactivity in the efferent endings at the base of OHCs and at the level of the OHC nucleus. At the base of OHCs, CGRP reactive endings in the first, second and more rarely the third row. CGRP immunoreactivity was localized in large dense core vesicles. In summary, our data demonstrate that the neuropeptide, CGRP, was found in both the lateral and medial efferent systems. Secondly, the immunoreactivity was localized in large dense core vesicles.

Animals↗

PubMed1992

Cholinergic regulation of the phosphoinositide second messenger system in the guinea pig organ of Corti.

The effect of cholinergic agents on the phosphoinositide second messenger system was investigated in the cochlea of the adult guinea pig in vivo and in vitro. In vivo, phospholipids were labeled with [32P]-orthophosphate by perilymphatic perfusion and their hydrolysis assayed in 'chase' experiments with non-radioactive orthophosphate. Carbachol (1 mM) reduced the content of 32P-labeled phosphatidylinositol 4,5-bisphosphate in the organ of Corti from 31% to 21% of total 32P-lipids, indicating stimulated hydrolysis. The pharmacology of this effect was studied in detail in vitro via the release of inositol phosphates from phosphoinositides pre-labeled with 3H-inositol. Release was increased 2-fold by 1 mM carbachol, 1.6-fold by 1 mM muscarine, but was unaffected by dimethylphenylpiperazinium; the stimulation was blocked by 1 microM atropine but not mecamylamine. These responses indicate the coupling of phosphoinositides to a muscarinic receptor. Furthermore, stimulated inositol phosphate release was higher in the base of the organ of Corti than in the apex which correlates with the increased cholinergic efferent innervation of outer hair cells in the basal region. These results suggest that muscarinic-stimulated inositol phosphate release occurs at the level of the outer hair cell and thus may have an important modulatory role in auditory transduction.

Animals↗

PubMed1999

Mechanically evoked shortening of outer hair cells isolated from the guinea pig organ of Corti.

Outer hair cells isolated from the mammalian hearing organ have been shown to respond to mechanical stimuli at acoustic frequencies by expressing a change in cell length (e.g. Canlon et al., 1988). The acoustically evoked response is characterised by both a tonic length change following the envelope of the stimulus, and a frequency-dependent phasic component. We show here that mechanical stimulation at much lower frequencies directed at the cell body also elicits length changes of the outer hair cells. When the apical pole of isolated outer hair cells was compressed with a quartz fibre, a shortening or contraction at the basal pole was observed. Transverse indentation at the lateral membrane elicited shortenings at both ends of the cells. The sensitivity to the mechanical manipulation was changed by an altered tonicity of the external solution, or exposure to salicylate. As the response occurs at very low stimulus frequencies, it may account for the mechanism by which the hearing organ responds to the low frequency modulation component in complex signals like speech.

Animals↗

PubMed1989

[Damage caused by endotoxin of the neural components of the organ of Corti].

The endotoxin (lipopolysaccharides, LPS) of H. influenzae extracted with phenol-water method was injected into the perilymphatic compartment of guinea pig via the round window membrane. The CAP thresholds of the cochleas injected with LPS rose to 70.00 +/- 21.76 dB. The N1 latency at threshold prolonged until 2.63 +/- 0.28 ms. Compared with the controls, the differences were significant statistically at the level of 1% and 5% respectively. Electron microscopy found that the neural fibers of the organ of Corti were swollen, organelles degenerated, axon atrophied and disappeared. The myelin sheaths collapsed. The organelles and vesicles in the synapses decreased and disappeared. The synaptic membrane destroyed. The results exhibited that the LPS of H. influenzae had toxic effects on the neural components of the organ of Corti and the degeneration of the neural components was the pathological basis of the elevation of CAP thresholds and the N1 latency delay. It is concluded that once endotoxin enters into the perilymphatic compartment, it not only causes physiological changes but results in irreversible alterations of the neural components pathologically.

Action Potentials↗

PubMed1998

Immunoelectron microscopic localization of nitric oxide synthase III in the guinea pig organ of Corti.

Nitric oxide synthase III (NOS III) was identified in the guinea pig cochlea on an ultrastructural level using a post-embedding immunolabeling procedure. Ultrathin sections of London Resin (LR) White-embedded specimens were incubated with various concentrations of a commercially available antibody to NOS III and the immunoreactivity visualized by a gold-labeled secondary antibody. Analysis of ultrathin sections of the organ of Corti in the second turn of the cochlea showed that NOS III could be localized in the endothelial cells of the blood vessels under the basilar membrane, which was comparable to its location in similar cells types in various biological systems. Besides this, NOS III was also found in the cytoplasm and in the nuclei of inner and outer hair cells. Immunoreactivity was not distributed homogeneously within receptor cells. Numerous gold particles could be identified at the border of the cuticular plates, in the middle parts of the stereocilia and in the cytoplasm. Gold-labeled anti-NOS III antibodies in these sites were seen mostly on the cytoplasmic side of the submembranous cisterns in the vicinity of mitochondria and in the central parts of the hair cells, whereas the cisterns were nearly free from any immunoreactivity. NOS III was also detected in the efferent and afferent nerve endings that were located at the basal and basolateral side of the outer hair cells. Some immunoreactivity was visible in different nerve fibers of the inner and outer spiral tunnels. Besides this, gold-labeled antibodies were also present in the cuticular plate of inner and outer pillar cells, in the cytoskeletal elements located in the apical parts of Deiters cells, forming the lamina reticularis, and in the cytoskeletal-containing region of the cytoplasm of those Deiters cells located at the basal side of the outer hair cells. The role of the NOS III immunoreactivity identified in the organ of Corti was consistent with respect to hair cell and tissue modulation.

Animals↗

PubMed2005

Transcriptional regulation by Barhl1 and Brn-3c in organ-of-Corti-derived cell lines.

Barhl1 and Brn-3c have been identified as transcription factors that are essential for survival and maintenance of hair cells of the inner ear. Little is known about the mechanism of how Brn-3c or Barhl1 may regulate transcription in the inner ear. In this study, the transcriptional function of both Brn-3c and Barhl1 was investigated in the organ-of-Corti-derived cell lines, OC-1 and OC-2. We examined regulatory domains in these transcription factors by linking regions of Barhl1 and Brn-3c to the DNA binding domain of the heterologous transcription factor GAL4 and assayed their effect on a heterologous promoter containing GAL4 DNA binding sites by co-transfection into OC-1 and OC-2 cell lines. Brn-3c was found to contain an independent N-terminal activation domain that is sufficient to activate gene transcription in the organ of corti derived cell lines. Barhl1 on the other hand was found to act as a transcriptional repressor with repressive activity not restricted to a particular domain of Barhl1. In addition, we analyzed the effect of Barhl1 on the promoters of the neurotrophin genes NT-3 and BDNF in OC-1 and OC-2 cell lines. However, Barhl1 was not found to directly regulate neurotrophin promoter constructs in these cells.

Animals↗

PubMed1996

Ultrastructural damage to the organ of corti during acute experimental Escherichia coli and pneumococcal meningitis in guinea pigs.

Experimental meningitis was induced in 16 pigmented guinea pigs by subarachnoid inoculation of mid log-phase 1 x 10(9) E. coli K-12 (n = 8) or 5 x 10(7) Streptococcus pneumoniae type 2 (n = 8). Animals were killed at various times between 3 and 12 h after inoculation and the ultrastructure of the organ of Corti (including the basilar membrane) was examined with high resolution scanning electron microscopy. Both E. coli and S. pneumoniae induced meningitis and invaded scala tympani. In both types of meningitis the apical surface of inner supporting cells developed craters. inner hair cell stereocilia were also disrupted. In pneumococcal meningitis both these lesions were more pronounced but in addition there were breaks in the junctions between inner hair cells and their adjacent supporting cells and there was ballooning and rupture of the apical surface of outer hair cells. Damage to the organ of Corti after bacterial invasion of the inner ear may be one of the mechanisms by which bacterial meningitis can cause deafness. The more severe cochlear lesions induced by S.pneumoniae may explain the higher incidence of deafness after pneumococcal meningitis.

Animals↗

PubMed1981

Some new aspects on damages in the organ of Corti after pure tone exposure.

(1) The loss of hair cells after pure tone exposure at the critical level of intensity shows an exact correlation to the frequency, the time of sound exposure, and time of recovery as regards the quality and quantity. (2) The total extent of the damage of sensory cells has to be estimated higher than the hair-cell loss as observed under the light microscope. Although an improvement of the function of the organ of Corti was determined electrophysiologically from the 5th to the 10th day of recovery, the hair-cell degeneration was progredient during this period. (3) The hair-cell damage is apically more strongly marked from the area of damage than basically. (4) Depending on the experimental conditions there are considerable degenerative alterations in the nerve fibres and in the connective apparatus of the organ of Corti besides hair-cell losses and damages.

Acoustic Stimulation↗

PubMed1990

Morphology of synapses at the base of hair cells in the organ of Corti of the chimpanzee.

The synaptic morphology of inner and outer hair cells of the organ of Corti of the chimpanzee was evaluated by serial section electron microscopy. The morphology of nerve terminals and synapses at both sites was very similar to that of human and other mammalian species. Two types of nerve terminals, nonvesiculated and vesiculated, with distinct synaptic morphology were found. In addition, between some nonvesiculated endings and outer hair cells, a reciprocal synaptic relationship was seen. In such terminals there was morphologic evidence for transmission from hair cell to neuron and from neuron to hair cell between a single neuron and an outer hair cell.

Animals↗

PubMed1982

Giant cilia in the human organ of Corti.

Fusion of cilia, the growth of clumps of fused cilia and giant cilium formation have been studied in the normal human organ of Corti using the scanning electron microscope. These unusual forms are found mainly in the apical portions of the cochlea and appear to precede the loss of normal apical cilia which increases and extends in a basal direction with age. These changes may be due to low frequency noise damage or be a phenomenom of ageing. The mechanism of their formation is discussed in the light of recent experimental work on cell fusion.

Adult↗

PubMedDate not supplied

Nerve fibers in the human organ of Corti.

In the human cochlea, the following characteristics of nerve fiber arrangements were observed. 1. Where there was only the basilar fiber in the tunnel of Corti, the internal and tunnel spiral bundle were not observed. In such cases, the number of nerve fibers in the external spiral bundle was small. 2. In the tunnel of Corti, the basilar fibers (afferent) took a course at the base and crossing the tunnel slanting to the basal end. 3. The medial fibers were present with the internal spiral bundle and tunnel spiral bundle. These fibers are possibly efferent. 4. The external spiral bundle increases its fiber count when internal and tunnel spiral bundles were present in the organ of Corti. 5. The external spiral bundle was composed of the basilar and medial fibers. The former were less and the latter much more numerous in the bundle. 6. 85-90% of the afferent fibers went to the internal hair cells, while the remainder went to the external hair cells. 7. The nerve fibers were found in the organ of Corti lateral to the external spiral bundles. The fibers were running in the Hensen's and Claudius' cell area. 8. In some cases medial fibers showed a torpedo-like deformity in the tunnel of Corti. When this was observed, it was found distributed throughout the entire cochlea. Hearing disorders due to this pathology of the efferent fiber was suggested.

Aged↗

PubMed1996

The alteration of ultrastructure and immunoreactivity of human embryonic organ of Corti tissue culture after exposure to aminoglycoside (neomycin) ototoxicity.

Using electron microscopy and GABA immunohistochemistry we evaluated the effects on human embyronic organ of Corti tissue culture of exposure to the ototoxic aminoglycoside antibiotic neomycin at a dose of 1 mM for 48 to 96 hrs. Neomycin induces the formation of multilamellar myeloid structures. These lesions, found only in the basal coil but both in inner and outer hair cells, were characteristic of the membrane-associated neomycin-induced damage. A large amount of lipofucsin and numerous lipoid vacuoles as well as vesicle-filled mound-like protrusions were also observed after exposure to neomycin. It seems there is no obvious effect on GABAergic innervation.

Aminoglycosides↗

PubMed1987

Preparation of the mammalian organ of Corti for scanning electron microscopy.

The effect of various standard tissue preparation procedures for scanning microscopy on the morphology of the mammalian organ of Corti has been examined. Comparison was made of (i) different fixatives: glutaraldehyde (GA) alone, osmium (Os) alone, GA and Os together and GA followed by Os; (ii) freeze-drying (FD) versus critical point-drying (CPD); (iii) ligand binding of osmium with thiocarbohydrazide (TOTO procedure) versus sputter coating to provide a conductive coat. Results were assessed in terms of known structural parameters in fresh tissue. It is shown: (i) that double fixation, either GA, Os together or GA followed by Os, consistently produced less tissue distortion than either fixative alone, (ii) that FD produced less shrinkage of the tissue than CPD, and (iii) that the TOTO procedure appeared to rigidify the tissue and enhanced preservation of the morphology.

Animals↗

PubMed1989

Observation of the glycocalyx of the organ of Corti: an investigation by electron microscopy in the normal and gentamicin-treated guinea pig.

The ultrastructure of the glycocalyx of the organ of Corti in the normal and gentamicin-treated guinea pig was investigated at the electron microscopic level by using the ruthenium red staining technique. The glycocalyx was evident over the whole apical surface of both sensory and supporting cells. The entire length of the stereocilia of both inner and outer hair cells was seen to be covered by a glycocalyx, which interconnected the neighbouring stereocilia. In the gentamicin-treated animals, the fusion process between the stereocilia was revealed and a decrease of the glycocalyx was noticed at the point where fusion started. These findings suggest that the glycocalyx may play an important role in holding the stereocilia together in a bundle, yet prevent their close contact by means of its strong negative charge.

Animals↗

PubMed1990

Partial amino acid sequence of organ of Corti protein OCP-II.

We have previously described two low-molecular-weight, highly acidic proteins which are present in the organ of Corti in extremely high concentrations. Since the function of these proteins is not known, they have been assigned the tentative names OCP-I and OCP-II. In the hope of obtaining information about their function through homology studies, we have initiated amino acid sequencing of these proteins. We have recently succeeded in obtaining a brief amino-terminal sequence of OCP-II. We now report on a significant extension of the amino-terminal sequence of OCP-II and our first results on sequences of peptide fragments obtained by limited digestion with V8 protease. Together, the sequenced segments account for about one-third of the total sequence. Comparisons with the sequences of known proteins suggest that OCP-II is not a structural protein, but that it may exhibit biologic activity.

Amino Acid Sequence↗

PubMed1995

Cloning of an organ of Corti anion exchanger 2 isoform with a truncated C-terminal domain.

We have isolated a cDNA clone from a guinea pig organ of Corti library encoding a new isoform of the Anion Exchanger 2 (AE2) protein. This cDNA clone shows an 83 bp deletion in the region that encodes the membrane domain of AE2. Analysis of the overlapping regions of genomic and cDNA clones indicates that the missing portion does not correspond exactly to a constitutive exon. The alternate splicing process that generates this transcript involves internal donor and acceptor sites which introduces a shift in the open reading frame. The resulting polypeptide has a conserved cytoplasmic N-terminal domain but the membrane C-terminal domain has only two of the fourteen membrane spanning regions. An affinity-purified antipeptide antibody to the novel C-terminus detects an 89 kDa polypeptide which agrees with the molecular mass predicted from the cDNA.

Amino Acid Sequence↗

PubMed1994

Localization of F-actin and fodrin along the organ of Corti in the chinchilla.

The distribution of the two cytoskeletal proteins, filamentous actin (F-actin) and fodrin, was investigated along the organ of Corti of the chinchilla using laser scanning confocal fluorescence microscopy. High intensity labeling of F-actin was seen in outer and inner hair cells, including the stereocilia. High intensity staining was also seen for fodrin in outer and inner hair cells, but not in their stereocilia. Staining intensity of both proteins along the lateral cell wall of the outer hair cells appeared to be greater in the middle and basal cochlear turns than in the apical turn. Pillars and Deiters cells also exhibited high intensity labeling of F-actin. The lack of significant differences in the distribution of fodrin between outer and inner hair cells makes the role of this protein in the active processes still unclear. Comparison of the distribution of F-actin and fodrin in the chinchilla with those reported in the guinea pigs suggest possible species differences.

Actins↗