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At least 19 recordsLinked to original sources
PubMed1996

Mechanical properties of the lateral cortex of mammalian auditory outer hair cells.

Mammalian auditory outer hair cells generate high-frequency mechanical forces that enhance sound-induced displacements of the basilar membrane within the inner ear. It has been proposed that the resulting cell deformation is directed along the longitudinal axis of the cell by the cortical cytoskeleton. We have tested this proposal by making direct mechanical measurements on outer hair cells. The resultant stiffness modulus along the axis of whole dissociated cells was 3 x 10(-3) N/m, consistent with previously published values. The resultant axial and circumferential stiffness moduli for the cortical lattice were 5 x 10(-4) N/m and 3 x 10(-3) N/m, respectively. Thus the cortical lattice is a highly orthotropic structure. Its axial stiffness is small compared with that of the intact cell, but its circumferential stiffness is within the same order of magnitude. These measurements support the theory that the cortical cytoskeleton directs electrically driven length changes along the longitudinal axis of the cell. The Young's modulus of the circumferential filamentous components of the lattice were calculated to be 1 x 10(7) N/m2. The axial cross-links, believed to be a form of spectrin, were calculated to have a Young's modulus of 3 x 10(6) N/m2. Based on the measured values for the lattice and intact cell cortex, an estimate for the resultant stiffness modulus of the plasma membrane was estimated to be on the order of 10(-3) N/m. Thus, the plasma membrane appears to be relatively stiff and may be the dominant contributor to the axial stiffness of the intact cell.

Animals↗
PubMed2000

Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic transmission at auditory outer hair cells.

Fast inhibitory synaptic transmission in the central nervous system is mediated by ionotropic GABA or glycine receptors. Auditory outer hair cells present a unique inhibitory synapse that uses a Ca2+-permeable excitatory acetylcholine receptor to activate a hyperpolarizing potassium current mediated by small conductance calcium-activated potassium (SK) channels. It is shown here that unitary inhibitory postsynaptic currents at this synapse are mediated by SK2 channels and occur rapidly, with rise and decay time constants of approximately 6 ms and approximately 30 ms, respectively. This time course is determined by the Ca2+ gating of SK channels rather than by the changes in intracellular Ca2+. The results demonstrate fast coupling between an excitatory ionotropic neurotransmitter receptor and an inhibitory ion channel and imply rapid, localized changes in subsynaptic calcium levels.

Animals↗
PubMed1999

Mechanical and electromotile characteristics of auditory outer hair cells.

The passive and active properties of the cochlear outer hair cell are studied. The outer hair cell is currently considered the major candidate for the active component of mammalian hearing. Understanding of its properties may explain the amplification and sharp frequency selectivity of the ear. To analyse the cell behaviour, a model of a nonlinear anisotropic electro-elastic shell is used. Using the data from three independent experiments, where the mechanical strains of the cell are measured, estimates of the cell wall in-plane Young's moduli and Poisson's ratios are given, as well as estimates of three modes of bending stiffness. Based on these estimates and data from the microchamber experiment, where the cell is under the action of transmembrane potential changes, the characteristics of the outer hair cell active behaviour are found. These characteristics include the coefficients of the active force production per unit of the transmembrane potential change and limiting parameters of the electromotile response for extreme hyperpolarisation and depolarisation of the cell. The obtained estimates provide important information for the modelling of organ-level cochlear mechanics.

Biomechanical Phenomena↗
PubMed1995

Organic material concentration in auditory outer hair cells measured by laser interferometry.

Outer hair cells (OHC) of the mammalian cochlea are quasicylindrical cells of different length, which play a major role in hearing at threshold. Their particular shape allows the use of a noninvasive laser interferometric technique of isolated cells in vitro in order to measure the organic material concentration (OMC), hence the density of each cell body. In most (95%) of the OHCs isolated from the same guinea pig, when the cell diameter is normalized, the results show that the cell body OMC does not vary with cell length. In different animals, the respective normalized OMC mean values can vary between 70 kg/m3 and 103 kg/m3. A few OHCs with morphological particularities often possess cell body OMCs > 103 kg/m3. The results of the interferometric measurements in isolated OHCs confirm that density variations in the cell bodies are not involved in a sound frequency coding. The in vitro OMC variations of the OHCs could be related to the isolation procedure; however, they could also correlate with actual in vivo OMC variations.

Animals↗
PubMed1996

Viscoelastic relaxation in the membrane of the auditory outer hair cell.

The outer hair cell (OHC) in the mammalian ear has a unique membrane potential-dependent motility, which is considered to be important for frequency discrimination (tuning). The OHC motile mechanism is located at the cell membrane and is strongly influenced by its passive mechanical properties. To study the viscoelastic properties of OHCs, we exposed cells to a hypoosmotic solution for varying durations and then punctured them, to immediately release the osmotic stress. Using video records of the cells, we determined both the imposed strain and the strain after puncturing, when stress was reset to zero. The strain data were described by a simple rheological model consisting of two springs and a dashpot, and the fit to this model gave a time constant of 40 +/- 19 s for the relaxation (reduction) of tension during prolonged strain. For time scales much shorter or longer than this, we would expect essentially elastic behavior. This relaxation process affects the membrane tension of the cell, and because it has been shown that membrane tension has a modulatory role in the OHC's motility, this relaxation process could be part of an adaptation mechanism, with which the motility system of the OHC can adjust to changing conditions and maintain optimum membrane tension.

Animals↗
PubMed1991

Stretch sensitivity of the lateral wall of the auditory outer hair cell from the guinea pig.

The inner and outer hair cells of the mammalian hearing organ are mechano-transducer cells. Here we report evidence that the lateral wall of outer hair cells (OHCs) is a mechano-receptor. This mechano-sensitivity appears to complement that of the stereocilia. Patch clamping studies showed that stretching of the membrane patches by suction at the pipette activated potassium channels with 130 pS unit conductance specifically localized in the lateral wall. Application of an osmotic tension to the entire cell membrane under whole-cell recording produced a 10 mV hyperpolarization. The reversal potential and the magnitude of the macroscopic current under voltage clamp were consistent with the single-channel properties of stretch-activated potassium channels. The elongated cylindrical cell body of the OHC is optimally positioned in the cochlea to sense axial force due to the vibrations of the basilar membrane during sound stimulation. This sensitivity can explain the production of a predominantly hyperpolarizing response to sound stimuli, unique to the OHC. Coupled with voltage-dependent OHC motility, the stretch-activated channels may play an important role in producing a mechanical feedback, an indispensable element in cochlear tuning.

Animals↗
PubMed1993

Effect of stress on the membrane capacitance of the auditory outer hair cell.

The membrane capacitance of the outer hair cell, which has unique membrane potential-dependent motility, was monitored during application of membrane tension. It was found that the membrane capacitance of the cell decreased when stress was applied to the membrane. This result is the opposite of stretching the lipid bilayer in the plasma membrane. It thus indicates the importance of some other capacitance component that decreases on stretching. It has been known that charge movement across the membrane can appear to be a nonlinear capacitance. If membrane stress at the resting potential restricts the movement of the charge associated with force generation, the nonlinear capacitance will decrease. Furthermore, less capacitance reduction by membrane stretching is expected when the membrane is already extended by the (hyperpolarizing) membrane potential. Indeed, it was found that at hyperpolarized potentials, the reduction of the membrane capacitance due to stretching is less. The capacitance change can be described by a two state model of a force-producing unit in which the free energy difference between the contracted and stretched states has both electrical and mechanical components. From the measured change in capacitance, the estimated difference in the membrane area of the unit between the two states is about 2 nm2.

Animals↗
PubMed1992

A membrane-based force generation mechanism in auditory sensory cells.

Auditory outer hair cells can elongate and shorten at acoustic frequencies in response to changes of plasma membrane potential. We show that this fast bidirectional contractile activity consists of an electromechanical transduction process that occurs at the lateral plasma membrane and can be activated and analyzed independently in small membrane patches inside a patch electrode. Bidirectional forces are generated by increases and decreases in membrane area in response to hyperpolarization and depolarization, respectively. We suggest that the force generation mechanism is driven by voltage-dependent conformational changes within a dense array of large transmembrane proteins associated with the site of electromechanical transduction.

Animals↗
PubMed2003

Auditory amplification: outer hair cells pres the issue.

Active feedback mechanisms in the ears of mammals amplify and tune the auditory response to sound stimuli, allowing these organisms to enjoy both exquisite sensitivity and sharp frequency selectivity. A requisite component of this feedback pathway has recently been identified. Targeted deletion of pres, the gene that encodes the novel membrane-bound motor protein prestin, has revealed a hundred-fold loss in hearing sensitivity suggesting that it might be part of the elusive cochlear amplifier.

Animals↗
PubMed1997

A quantitative comparison of mechanoelectrical transduction in vestibular and auditory hair cells of neonatal mice.

Vestibular hair cells (VHCs) and cochlear outer hair cells (OHCs) of neonatal mice were stimulated by a fluid jet directed at their stereociliary bundles. Relations between the force exerted by the jet, bundle displacement, and the resulting transducer current were studied. The mean maximum transducer conductance in VHCs (2.6 nS) was about half that of the OHCs (5.5 nS), with the largest recorded values being 4.1 nS and 9.2 nS, respectively. In some OHCs activity of a single, 112 pS transducer channel was observed, allowing an estimate of the maximum number of channels: up to 36 in VHCs and 82 in OHCs, corresponding to about one transducer channel per tip link. The VHC bundles required about 330 nm of tip displacement to activate 90% of the maximum transducer conductance, compared to 150 nm for the OHC bundles. This corresponded to 2 deg of rotation about their pivots for both, due to the greater length of the VHC bundles. The VHC bundles' translational stiffness was one-seventh of that of the OHCs. Conversion to rotational stiffness almost abolished this difference. Rotation of the hair bundle rather than translation determines the gating of the transducer channels, independent of bundle height or origin of the cells.

Animals↗
PubMedDate not supplied

Cytoskeletal basis for contractility of outer hair cells in the normal adult human organ of Corti: comparisons with vestibular hair cells.

The present study is the first consecutive analysis of the adult normal human organ of Corti and vestibular hair cells with regard to the expression of F-actin, actin-associated proteins (alpha-actinin, alpha- and beta-spectrins, vinculin and tropomyosin), beta-tubulin and the calcium-binding protein synaptophysin. The expression of these cytoskeletal and their associated proteins in man is largely similar to, although not identical with, that previously described for several other mammalian species. However, a few very unusual staining patterns were found. In several long outer hair cells a rod of F-actin extended from the infracuticular area to the cell nucleus. Fluorescence for tropomyosin occurred both in the cuticular plates of the outer and inner hair cells, and in the area of close apposition between the base of the outer hair cell and the apical part of Deiter's cell. In contrast, the vestibular hair cells showed immunoreactivity for tropomyosin only in the cuticular plates.

Actinin↗
PubMedDate not supplied

Calbindin-D28K localization in the primate inner ear.

The distribution of one of the calcium-binding proteins, calbindin-D28K (CB-D28K), was studied in the adult human and squirrel monkey inner ear by means of immunocytochemical methods. Inner and outer hair cells in the organ of Corti and vestibular hair cells showed CB-D28K immunoreactivity, though some vestibular hair cells were devoid of immunoreactivity. In the spiral and vestibular ganglion, immunoreactive cells were found in both the squirrel monkey and human. The present results indicate that CB-D28K is localized within afferent neuronal components in these sensory organs and may regulate Ca++ levels for optimal neurotransmission in the primate auditory and vestibular systems. This study also provides evidence of two nonneuronal localizations of CB-D28K in the squirrel monkey. Subpopulations of fibrocytes in the spiral ligament and vestibular end organs were enriched with CB-D28K, suggesting that these cells are possibly equipped with the function to regulate Ca++ concentration in the perilymphatic fluid. In the maculae, many CB-D28K-immunoreactive particles were found in the otoconial membrane, indicating that CB-D28K may participate in the formation of otoconia.

Adolescent↗
PubMed2000

Alpha and beta subunits of acetylcholine receptors in the human inner ear.

The localization and distribution of nicotinic acetylcholine receptors (n-ACh-r) was characterized by studying alpha and beta subunits in the adult human inner ear by FITC fluorescence technique. In the cochlea, distinct fluorescence staining occurred for beta subunits in outer hair cells (OHCs), but no alpha subunits were identified. Beta subunits differ quantitatively between the three rows of OHCs, decreasing along a base-to-apex gradient in the cochlea. Both alpha and beta subunits were identified on spiral ganglion cells, adjacent nerve fibres and in vestibular hair cells (HCs). It would appear that they form an active complex in n-ACh-r at these locations.

Adolescent↗
PubMedDate not supplied

Microtubule-associated proteins in adult human sensory organs.

The distribution of microtubule-associated proteins MAP-1 and MAP-2 was analysed with immunomorphological techniques in the serially sectioned adult human membranous labyrinth. In the organ of Corti, monoclonal antibodies to MAP-1 did not stain. Positivity for MAP-2 occurred in the entire outer hair cell cytoplasm, in the inner hair cells (?), in the nerve fibres and in the cytoplasm of epithelial cells of the spiral prominence. In addition, staining for MAP-2 was identified in many (but not all) cells or Reissner's membrane. Immunofluorescence for MAP-1 occurred in the supporting cells of the cristae and maculae interpreted to be localized in the apical region adjacent to the sensory cells. Thus, the distribution of MAP-1 and MAP-2 in the adult human membranous labyrinth was the same as described for several animal species with regard to the cochlea. In contrast to such a pattern, both MAP-1 and MAP-2 were identified in the human vestibular organs, thus identifying a subpopulation of centrally located nerve calyces and possibly also the apical portion of vestibular hair cells.

Acoustic Maculae↗
PubMed2000

Gating energies and forces of the mammalian hair cell transducer channel and related hair bundle mechanics.

We quantified the molecular energies and forces involved in opening and closing of mechanoelectrical transducer channels in hair cells using a novel generally applicable method. It relies on a thermodynamic description of the free energy of an ion channel in terms of its open probability. The molecular gating force per channel as reflected in hair bundle mechanics is shown to equal kT/I(X) x dI(X)/dX, where I is the transducer current and X the deflection of the hair bundle. We applied the method to previously measured I(X) curves in mouse outer hair cells (OHCs) and vestibular hair cells (VHCs). Contrary to current models of transduction, gating of the transducer channel was found to involve only a finite range of free energy (< 10 kT), a consequence of our observation that the channel has a finite minimum open probability of ca. 1% for inhibitory bundle deflections. The maximum gating forces per channel of both cell types were found to be comparable (ca. 300-500 fN). Because of differences in passive restoring forces, gating forces result in very limited mechanical nonlinearity in OHC bundles compared to that in VHC bundles. A kinetic model of channel activation is proposed that accounts for the observed transducer currents and gating forces. It also predicts adaptation-like effects and spontaneous bundle movements ensuing from changes in state energy gaps possibly related to interactions of the channel with calcium ions.

Animals↗
PubMedDate not supplied

Hyaluronic acid as a molecular filter and friction-reducing lubricant in the human inner ear.

Immunofluorescence for hyaluronic acid occurred intracellularly in morphologically highly specialized areas in the adult human inner ear, for instance in the cuticular plates of all types of hair cells, at the apposition between outer hair cells and Deiter's cell bodies and in the near-surface area of Hensen's cells. The cytoskeletal organization in these regions is characterized by tightly packed filamentous proteins. Under physiological stimulus these regions undergo micromechanical change, either actively moving (force generation) or passively vibrating with changes in elasticity. Hyaluronic acid might therefore act as a friction-reducing molecular lubricant. In the lateral wall of the cochlea an accumulation of hyaluronic acid occurred in the loose connective tissue of the spiral ligament, in particular close to the stria vascularis. Due to its complex molecular network, hyaluronic acid offers considerable resistance to bulk flow of water and may exclude molecules. The basal cell region of the stria vascularis is thus given additional support to minimize (seal?) the stria vascularis towards all other areas except the endolymphatic space. Here, hyaluronic acid could act as a molecular filter.

Adolescent↗
PubMed1999

Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection.

Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.

Action Potentials↗