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PubMed1990

Synaptic morphology of inner and outer hair cells of the human organ of Corti.

Innervations of inner and outer hair cells of the organ of Corti of the human cochlea were studied by serial section electron microscopy. At the base of inner hair cells, presumed afferent fibers were of varying size and demonstrated synaptic specialization consisting of a presynaptic body, vesicles, and asymmetrical synaptic membrane specialization. Two types of neurons, vesiculated presumably efferent and nonvesiculated presumably afferent, synapsed at the base of outer hair cells. The synaptic specialization of afferent fibers included presynaptic body, vesicles, and asymmetrical membrane thickening, whereas efferent synapses demonstrated presynaptic vesicles and a subsynaptic cisterna. Some presumably afferent nerve terminals formed a reciprocal synapse with outer hair cells in both the human and the chimpanzee. Such a synaptic relationship demonstrated morphologic specialization consistent with both hair cell-to-neuron and neuron-to-hair cell transmission between the same outer hair cell and nerve terminal. The innervation density of inner and outer hair cells and the comparative anatomy of the afferent and efferent innervation are discussed.

Animals↗
PubMed1990

Influence of membrane surface potential and of net charge on aminoglycoside binding to the organ of Corti of guinea pigs.

Gentamicin binding to homogenates of the organ of Corti of guinea pigs was investigated by altering the magnitude of the membrane surface potential and by testing the potencies of various polyamines and polyamino acids with different numbers of amino groups and different net charge to inhibit or displace bound gentamicin. Diminishing or increasing the ionic strength of the milieu resulted in an increase and a decrease in drug binding, respectively. This observation may be accounted for by the negativity of the membrane surface potential which was enhanced or reduced, when the concentration of cations in the milieu was decreased or increased, respectively. Polyamines and polyamino acids displaced bound gentamicin and inhibited gentamicin binding as a function of the number of amino groups present within the molecule and of their cationic nature. These results point out the importance of considering the surface potential of biological membranes and the net positive charge of the drug in estimating its affinity for the binding site.

Animals↗
PubMed1997

Localization of organ of Corti protein II in the adult and developing gerbil cochlea.

The distribution of organ of Corti protein II (OCP-II) was assessed in the developing and mature gerbil cochlea by light and electron microscopic immunohistochemistry. In the adult cochlea, OCP-II was expressed only in certain epithelial cells which included all supporting cells of the organ of Corti, inner and outer sulcus cells and interdental cells. Inner and outer hair cells lacked immunoreactivity. The highest gold particle labeling density was seen overlying intracellular regions devoid of organelles. In the developing inner ear, OCP-II was first detected at 2 days after birth (DAB) with the strongest staining in immature Deiters, inner phalangeal and pillar cells. Immunostaining intensity increased gradually in cells lying laterally and medially to the more centrally located supporting cells and reached adult levels in all reactive cell types around 18 DAB. The results demonstrated conclusively that OCP-II is a cytosolic protein and fail to support its role as a transcription factor postulated on the basis of its homology with p15 or a role in the control of the cycle as suggested by its near-identity with p19Skp1, a cyclin A/CDK2-associated protein. The continued high level of expression in the mature cochlea argues against OCP-II's involvement in regulating the development and differentiation of epithelial cells. The protein's unique distribution and its gradual increase in expression prior to and during the onset and maturation of hearing, however, support its potential function in the recycling of K+ effluxed from hair cells and neurons back to endolymph.

Acoustic Stimulation↗
PubMed1998

Novel variant of the P2X2 ATP receptor from the guinea pig organ of Corti.

ATP functions as a neurotransmitter and a neuromodulator in various tissues by acting on metabotropic (P2Y) and ionotropic (P2X) receptors. Evidence suggests that ATP activates P2X receptors on several cell types in the organ of Corti of guinea pig including outer hair cells (OHCs), Deiters' cells, Hensen's cells, pillar cells and inner hair cells (IHCs). Determining the sequence and structure of P2X receptors in guinea pig organ of Corti is important for understanding the function of ATP in the cochlea. We screened a guinea pig organ of Corti cDNA library for P2X2 ATP receptors using rat P2X2 cDNA as a probe. We sequenced three P2X2 variants which were found to be abundant in this library. One is a novel P2X2 isoform (P2X2-3) created by a retained intron coding for an additional 27 amino acids (81 bp) in the putative extracellular domain. We have also sequenced a variant (P2X2-2) that lacks both the 81-bp sequence and a 192-bp sequence in the 3' intracellular domain. A third variant (P2X2-1) contains the intracellular 192-bp sequence but not the extracellular 81-bp sequence found in P2X2-3. The multiple transcripts arise from alternative intron and exon splicing events. In situ hybridization with a probe common to the three variants localized P2X2 to many of the cells of the organ of Corti.

Adenosine Triphosphate↗
PubMed1997

Intermodulation components in inner hair cell and organ of Corti responses.

Two-tone responses are recorded from inner hair cells and from the organ of Corti fluid space in second and third turns of the guinea pig cochlea where best frequencies (BF) are approximately 4000 and 1000 Hz, respectively. This allows both ac and dc response components to be obtained and facilitates comparisons with psychophysical investigations that have traditionally been conducted at low and moderate frequencies. The measurements of ac responses in the organ of Corti fluid space also allow comparisons with mechanical results because the cochlear microphonic is proportional to basilar membrane displacement. By using a constant frequency ratio (f2/f1) of 1.4, local distortion products generated at the recording location are prominent when the two primaries are near the BF of the cell. However, when the primary pairs increase above BF, quadratic and cubic difference tones are recorded even when responses to the primaries are not measurable. The presence of these traveling distortion products is consistent with the idea that both f2-f1 and 2f1-f2 have their own traveling waves. Notches in the existence regions of quadratic and cubic difference tones were also observed and found to be influenced by mutual suppression between the two inputs.

Acoustic Stimulation↗
PubMed1992

Ultrastructure of the horseshoe bat's organ of Corti. II. Transmission electron microscopy.

The fine structure of the organ of Corti was investigated in the echolocating horseshoe bat (Rhinolophus rouxi) by transmission electron microscopy. Particular emphasis was placed on the receptor cells and their supporting cells. The receptor cells, inner hair cells (IHC) and outer hair cells (OHC), possess the typical mammalian shape, but OHCs are extremely short (length: 12-15 microns in the basal turn and up to 28-30 microns in the apical turn). The afferent innervation of both types of receptor cells and the efferent innervation of the IHC system conform to the general mammalian scheme; however, confirming earlier reports, an efferent innervation to the OHCs is absent. Throughout the cochlea, IHCs and OHCs possess a single layer of subsurface cisternae. Above the level of the nucleus of the OHCs, the arrangements of the subsurface cisternae and their connection to the lateral cell membrane via pillars are highly regular, whereas in IHCs, the cisternae are of irregular shape and the pillar system is much less distinct. In the basal turn of the cochlea, the attachment sites of the OHCs to the supporting cells possess specialized features: (a) in the reticular lamina, the contact sites of the cuticular plates of OHCs with the outer pillar cells and the Deiters cell phalanges are of exaggerated length, and (b) the cup formation of the Deiters cell body, which houses the bottom of the OHC, has a specialized shape and is packed with electron-dense material and microtubules. The results are discussed in relation to cochlear ultrastructure in other mammals and in the context of active processes in cochlear mechanics.

Afferent Pathways↗
PubMed1999

Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti.

Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B., et al. (1995) Science 267, 1024-1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27(Kip1) is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27(Kip1)-gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27(Kip1)-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

Acoustic Stimulation↗
PubMed1992

[Normal structure of stereocilia and recovery from ciliary damage in the organ of Corti after acoustic overstimulation].

The normal structure of outer hair cell (OHC) stereocilia in the organ of Corti, as well as damage and the recovery of OHC stereocilia after acoustic overstimulation, were demonstrated using scanning electron microscopy and tannic acid-osmium staining techniques. The highest row of OHC stereocilia is known to show an orderly gradation in height along the length of the cochlea. The present study demonstrated that the middle and lower rows of stereocilia possess a similar height gradation pattern. These findings suggest that the orderly gradation of stereocilia may play an important role in the tuning capability of the organ of Corti sensory cell. To investigate the mechanisms of recovery from ciliary acoustic damage, guinea pigs were exposed to a 4.00 kHz pure tone at an intensity of 120 dB for 120 minutes. All animals showed temporarily elevated hearing thresholds, which had returned to normal one week later. The first detectable change after acoustic overstimulation was a derangement of the cilia with a loss of ciliary interconnections. The tip links connecting the tips of the stereocilia to their taller neighbours were also affected showing elongation or disappearance. In comparing ciliary damage immediately after and one week after acoustic overstimulation, no signs of recovery in hair cell cilia which had been already lost, could be detected, while stereocilia with slight damage seemed to recover in the early post-sound exposure stage. Some lost tip links also seem to reappear in surviving cilia. In addition side links have the possibility of recovery.

Acoustic Stimulation↗
PubMed1999

Expression pattern of adenylyl cyclase isoforms in the inner ear of the rat by RT-PCR and immunochemical localization of calcineurin in the organ of Corti.

Most studies concerning adenylyl cyclases in the inner ear were carried out before the advent of molecular biology. In a PCR approach using cDNAs of six inner ear tissues (stria vascularis, endolymphatic sac, organ of Corti, vestibulum, cochlear and vestibular nerve) we found tissue specific expression of adenylyl cyclase isoforms. Adenylyl cyclases types 2 and 4 are predominant in the fluid controlling tissues, i.e. in the stria vascularis and endolymphatic sac. In the organ of Corti and vestibulum the Ca2+-modulated isoforms types 1, 6 and 9 were expressed. The regulation of adenylyl cyclase 9, which is the major isoform expressed in the organ of Corti, proceeds via the Ca2+-activated protein phosphatase 2B (calcineurin, PPP3). PCR with specific primers for calcineurin demonstrated its abundant expression in the organ of Corti. Using a monoclonal antibody we localized calcineurin immunochemically to the cochlear nerve, the nerve fibers and the inner hair cells. In the cochlear and vestibular nerves a characteristic neuronal expression pattern of adenylyl cyclase isoforms was observed, i.e. adenylyl cyclases types 2, 3 and 8. The functional consequences of the adenylyl cyclase expression pattern in the inner ear are discussed in conjunction with its unique sensory performance.

Adenylyl Cyclases↗
PubMed1989

The nature and progression of injury in the organ of Corti during ischemia.

This study has defined the nature and sequence of ultrastructural changes in the organ of Corti following severe, total cochlear ischemia. Afferent nerve endings of IHC became swollen within 15 min and eventually ruptured. Outer hair cells were swollen within 30 min and showed alterations to mitochondria, endoplasmic reticulum and the nucleus whereas IHC remained unchanged for up to 60 min. Both efferent and afferent nerve endings of OHC were unaltered until after 60 min ischemia. Regardless of the type, cells in the base of the cochlea developed abnormalities more rapidly than those in the apical turns. These results imply a differential susceptibility to ischemic damage both among the different cell types and along the organ of Corti.

Afferent Pathways↗
PubMed1982

Effects of altering organ of Corti on cochlear distortion products f2 - f1 and 2f1 - f2.

1. Single cochlear nerve fiber recordings from unexposed chinchillas show spatial distributions of amplitude and phase of the distortion products f2 - f1 and 2f1 - f2 similar to those previously reported for the cat (35, 37, 42). 2. Damaging the organ of Corti in the region corresponding to the frequencies of a two-tone stimulus substantially reduces the amplitude of these distortion products at their characteristic places. 3. The distortion products 2f - f1 and 2f1 - f2 thus appear to be generated in the organ of Corti in the region of the primary-frequency places. 4. The neural responses suggest that the distortion products are propagated in the motion of the cochlear partition like externally applied stimulus tones at the distortion frequencies wih a similar spatial distribution of distortion product amplitude and phase. Models of the cochlea that assume nonlinear cochlear-partition dynamics can account for the similarity by demonstrating that distortion products generated by cochlear-partition nonlinearity can propagate apicalward in the motion of the cochlear partition. 5. Models of the cochlea using a linear-system model for cochlear partition motion, in cascade with a nonlinear transduction stage and a subsequent sharp filter, are inadequate to account for present observations, unless two currently implausible assumptions are made: a) stimulus tones near 4 kHz must propagate in normal cochleas at least as far apically as the 300-Hz place with sufficient amplitude to generate f2 - f1 there, and b) damage to the organ of Corti must interfere with this propagation of 4-kHz stimulus tones to the 300-Hz place. 6. Distortion generation in the cochlea is sensitive to delicate alterations of the organ of Corti. Short moderate-intensity exposures to sound can reversibly reduce the amplitudes of the distortion products f2 - f1 and 2f1 - f2 seen in responses from cochlear nerve fibers with characteristic frequencies (CF) near the distortion frequencies. Since such exposures do ot produce permanent structural changes visible under light microscopy, it seems most reasonable to believe that subtle changes in the organ of Corti (most likely in the hair cells themselves) in the region most responsive to f1 and f2 reduce the generation of mechanically present distortion products.

Acoustic Stimulation↗
PubMed2002

Gene transfer into supporting cells of the organ of Corti.

To utilize the rapidly accumulating genetic information for developing new therapeutic technologies for inner ear disease, it is necessary to design technologies for expressing transgenes in the inner ear, especially in the organ of Corti. We examined the outcome of an adenovirus gene transfer into the organ of Corti via the scala media in guinea pigs. The transgene insert is the bacterial lacZ gene driven by a cytomegalovirus promoter. We demonstrate that the inoculation is detrimental to the hair cells that surround the site of inoculation, but the supporting cells in the organ of Corti survive and retain the ability to express the reporter transgene beta-gal. The ability to deliver transgenes that are expressed in the supporting cells is an important step in the development of clinically applicable treatments that involve hair cell regeneration.

Adenoviridae↗
PubMed1995

Ultrastructural detection of glycogen in the supporting cells of the organ of Corti with the periodic acid-thiocarbohydrazide-silver proteinate method.

The glycogen content of several types of supporting cells in the organ of Corti of the rat was demonstrated histochemically at the ultrastructural level using the periodic acid-thiocarbohydrazide-silver proteinate method. The development of the glycogen stores was assessed by means of a semiquantitative method in normal and congenitally-hypothyroid rats. At birth, all the cell types of the developing organ of Corti showed in their cytoplasms numerous glycogen particles. As development proceeded, the density of glycogen particles increased, reaching the highest value at the 8th postnatal day for the cells of the organ of Kölliker, inner pillar cell and outer pillar cell. On the other hand, the peak of maximum glycogen content in Deiters' cells was accomplished at the 15th postnatal day. From the day in which the maximum value was obtained onwards, the glycogen content in all the cell types fell and disappeared. Congenital hypothyroidism induced by propylthyouracil only affected the normal development of the density of glycogen particles in Deiters' cells, which didn't undergo the increase observed in the normal animals, remaining at values similar to those obtained at birth. This finding, together with previous similar results on the glycogen content of the inner ear's outer hair cells suggest that hypothyroidism selectively impairs the development of those organ of Corti's cells which mature on the second postnatal week, in the rat.

Animals↗
PubMed1976

Intercellular junctions in the reticular lamina of the organ of Corti.

Junctions between the cells in the reticular lamina of the organ of Corti were examined in thin sections and after freeze-fracturing to find a structural basis for the large ionic differences between the endolymph and perilymph. The apices of the cells in the reticular lamina are joined by a band of tight junctions spaced at 140 A intervals. Beneath this apical band the organization of the tight junctions depends on whether they join a supporting cell and a hair cell, or two supporting cells. At hair cell junctions with supporting cells, there is an extensive labyrinth of tight junctions enclosing lengthy, tortuous passages whose walls are composed of either multiple parallel or single junctions. At appositions between two supportinc cells, maculae or fasciae occludentes lie immediately beneath the apical bands of closely spaced tight junctions, near the top of the zonulae adherentia which are characteristic of appositions between supporting cells. The complexes of tight junctions, or zonulae occludentes, between extralaminar supporting cells differ from those in the reticular lamina. The extralaminar cells are joined by a band of four to seven branching, anastomotic tight junctions. Thus, these junctions are like zonulae occludentes in other tissues. The novel organizations of the tight junctions in the reticular lamina, different from those between the extralaminar supporting cells, suggests a special role for these junctions in the reticular lamina. Two sizes of gap junctions link, and presumably couple, supporting cells in the reticular lamina.

Animals↗
PubMed2003

[The protection of Tiron to the injury of organ of Corti cultured in vitro caused by exogenous H2O2 in mouse].

OBJECTIVE: In order to observe the action of H2O2 on inner and outer hair cells of organ of Corti in mouse, and discuss whether Tiron can effectively resistant the injury of free radicals in cultured cochlea in vitro or not. METHOD: Using the culture technology of organ of Corti in newborn mouse in vitro, established the model of the injury of inner and outer hair cells caused by exogenous H2O2. And observed the protection to the damage by H2O2 at different concentration of Tiron. RESULT: When the concentration of H2O2 is higher than 1.0 mmol/L, the loss of hair cells in the bottom, middle, and parietal turn of basilar membrane vary, the injury of bottom turn is more severe. In lower than 0.5 mmol/L group, the injury of hair cells is no relationship with the location. Adding Tiron (10 mmol/L) in culture can apparently decrease the injury of hair cells caused by H2O2. When the concentration of H2O2 is 0.01-1.0 mmol/L, Tiron can almost inhibit the loss of hair cells completely. CONCLUSION: There is apparently preventive effection of Tiron on organ of Corti cultured in vitro, and the mechanism of inhibiting injury caused by H2O2 is probably by clearing O2- and combining irony ion.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMedDate not supplied

Intercellular junctions in the organ of Corti.

The intercellular junctions between adjacent supporting cells and between apposed hair and supporting cells in the organ of Corti of cat and human were studied. At the endolymphatic surface, the intercellular space was closed by a series of tight junctions (zonula occludens), whereas there were no tight junctions at the basilar membrane surface of the neuroepithelium. Beneath the adlumenal zonula occludens between adjacent supporting cells, a zonula adherens (intermediate junction, "desmosone") was found. Many gap junctions joined apposed supporting cells both within apposed hair and supporting cells, membrane specialization sharing the morphological characterics of both the macula adherens and zonula adherens was found. Between cells, there were short areas of parallel limiting membranes separated by a 20A intercellular space. These areas were suggestive but not characteristic of gap junctional specialization. The functional significance of the junctional specialization between cells in the organ of Corti is discussed.

Animals↗
PubMed1995

The possible relationship between transient evoked otoacoustic emissions and organ of Corti irregularities in the guinea pig.

Otoacoustic emissions are believed to arise from an active process associated with the outer hair cells in the mammalian organ of Corti. They have been attributed to the presence of impedance discontinuities on the basilar membrane which might be caused by hair cell irregularities. To test this hypothesis we have investigated the possible relationship between transient evoked otoacoustic emissions (TEOAEs) and anatomical integrity in the organ of Corti. Click-evoked TEOAEs have been measured from the ear canals of normal, pigmented guinea pigs using an Otodynamics ILO88 analyser. Emissions were present in 18 out of 19 animals tested and the major frequencies observed were consistently present in different measurements over periods of up to ten weeks provided recording conditions were satisfactory. The frequency spectra of the TEOAEs resembled those measured in humans but the latencies of the responses were considerably shorter. In one acute experiment, the TEOAEs were shown to be dependent on metabolic energy as they were lost rapidly following termination with an overdose of anaesthetic. In another case, evoked emissions of long duration (sustained) at about 1 kHz were obtained from both ears. All cochleae examined showed irregularities, especially patches of mainly apical outer hair cell loss of differing extents. However, there was no evidence that substantial lesions coincided consistently with the frequency regions corresponding to the major emissions. Nevertheless, it was noted that the total energy level of emissions was proportional to the total outer hair cell loss, except in one case, where the outer hair cell loss was substantial and the energy level of TEOAEs was considerably lower. Although there is no clear relationship between TEOAEs of specific frequencies and abnormalities at the corresponding cochleotopic location in the organ of Corti which could represent impedance discontinuities, the degree of irregularity may determine the overall emission level. This finding is consistent with the idea that emissions arise as a result of irregularity producing variations in the reflection coefficient.

Acoustic Stimulation↗
PubMed1996

A novel zinc finger gene preferentially expressed in the retina and the organ of Corti localizes to human chromosome 12q24.3.

A cDNA encoding a novel member of the zinc finger gene family, designated zfOC1, has been cloned from the organ of Corti. This is the first transcriptional regulator cloned from this sensory epithelium. This transcript encodes a peculiar protein composed of 9 zinc finger domains and a few additional amino acids. The deduced polypeptide shares 66% amino acid similarity with MOK-2, another protein of only zinc finger motifs and preferentially expressed in transformed cell lines. Northern blot hybridization analysis reveals that zfOC1 transcripts are predominantly expressed in the retina and the organ of Corti and at lower levels in the stria vascularis, auditory nerve, tongue, cerebellum, small intestine and kidney. The human gene was mapped, using a human x hamster somatic cell hybrid panel and fluorescent in situ hybridization, to chromosome 12q24.3. Because of its relative abundance in sensorineural structures (retina and organ of Corti), this regulatory gene should be considered a candidate for hereditary disorders involving hearing and visual impairments that link to 12q24.3.

Amino Acid Sequence↗