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MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca²⁺ near stereocilia.

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The aim was to determine whether detachment of the tectorial membrane (TM) from the organ of Corti in Tecta/Tectb^-/- mice affects the biophysical properties of cochlear outer hair cells (OHCs). Tecta/Tectb^-/- mice have highly elevated hearing thresholds, but OHCs mature normally. Mechanoelectrical transducer (MET) channel resting open probability (P_o ) in mature OHC is ∼50% in endolymphatic [Ca²⁺ ], resulting in a large standing depolarizing MET current that would allow OHCs to act optimally as electromotile cochlear amplifiers. MET channel resting P_o in vivo is also high in Tecta/Tectb^-/- mice, indicating that the TM is unlikely to statically bias the hair bundles of OHCs. Distortion product otoacoustic emissions (DPOAEs), a readout of active, MET-dependent, non-linear cochlear amplification in OHCs, fail to exhibit long-lasting adaptation to repetitive stimulation in Tecta/Tectb^-/- mice. We conclude that during prolonged, sound-induced stimulation of the cochlea the TM may determine the extracellular Ca²⁺ concentration near the OHC's MET channels.

Abstract

The tectorial membrane (TM) is an acellular structure of the cochlea that is attached to the stereociliary bundles of the outer hair cells (OHCs), electromotile cells that amplify motion of the cochlear partition and sharpen its frequency selectivity. Although the TM is essential for hearing, its role is still not fully understood. In Tecta/Tectb^-/- double knockout mice, in which the TM is not coupled to the OHC stereocilia, hearing sensitivity is considerably reduced compared with that of wild-type animals. In vivo, the OHC receptor potentials, assessed using cochlear microphonics, are symmetrical in both wild-type and Tecta/Tectb^-/- mice, indicating that the TM does not bias the hair bundle resting position. The functional maturation of hair cells is also unaffected in Tecta/Tectb^-/- mice, and the resting open probability of the mechanoelectrical transducer (MET) channel reaches values of ∼50% when the hair bundles of mature OHCs are bathed in an endolymphatic-like Ca²⁺ concentration (40 μM) in vitro. The resultant large MET current depolarizes OHCs to near -40 mV, a value that would allow optimal activation of the motor protein prestin and normal cochlear amplification. Although the set point of the OHC receptor potential transfer function in vivo may therefore be determined primarily by endolymphatic Ca²⁺ concentration, repetitive acoustic stimulation fails to produce adaptation of MET-dependent otoacoustic emissions in vivo in the Tecta/Tectb^-/- mice. Therefore, the TM is likely to contribute to the regulation of Ca²⁺ levels around the stereocilia, and thus adaptation of the OHC MET channel during prolonged sound stimulation.

SUBMITTER: Jeng JY

PROVIDER: S-EPMC7612128 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:The purpose of this study was to analyze distortion product otoacoustic emission (DPOAE) level and signal to noise ratio in a group of infants from birth to 4 months of age to optimize prediction of hearing status. DPOAEs from infants with normal hearing (NH) and hearing loss (HL) were used to predict the presence of conductive HL (CHL), sensorineural HL (SNHL), and mixed HL (MHL). Wideband ambient absorbance was also measured and compared among the HL types. DESIGN:This is a prospective, longitudinal study of 279 infants with verified NH and HL, including conductive, sensorineural, and mixed types that were enrolled from a well-baby nursery and two neonatal intensive care units in Cincinnati, Ohio. At approximately 1 month of age, DPOAEs (1-8?kHz), wideband absorbance (0.25-8?kHz), and air and bone conduction diagnostic tone burst auditory brainstem response (0.5-4?kHz) thresholds were measured. Hearing status was verified at approximately 9 months of age with visual reinforcement audiometry (0.5-4?kHz). Auditory brainstem response air conduction thresholds were used to assign infants to an NH or HL group, and the efficacy of DPOAE data to classify ears as NH or HL was analyzed using receiver operating characteristic (ROC) curves. Two summary statistics of the ROC curve were calculated: the area under the ROC curve and the point of symmetry on the curve at which the sensitivity and specificity were equal. DPOAE level and signal to noise ratio cutoff values were defined at each frequency as the symmetry point on their respective ROC curve, and DPOAE results were combined across frequency in a multifrequency analysis to predict the presence of HL. RESULTS:Single-frequency test performance of DPOAEs was best at mid to high frequencies (3-8?kHz) with intermediate performance at 1.5 and 2?kHz and chance performance at 1?kHz. Infants with a conductive component to their HL (CHL and MHL combined) displayed significantly lower ambient absorbance values than the NH group. No differences in ambient absorbance were found between the NH and SNHL groups. Multifrequency analysis resulted in the best prediction of HL for the SNHL/MHL group with poorer sensitivity values when infants with CHL were included. CONCLUSIONS:Clinical interpretation of DPOAEs in infants can be improved by using age-appropriate normative ranges and optimized cutoff values. DPOAE interpretation is most predictive at higher F2 test frequencies in young infants (2-8?kHz) due to poor test performance at 1 to 1.5?kHz. Multifrequency rules can be used to improve sensitivity while balancing specificity. Last, a sensitive middle ear measure such as wideband absorbance should be included in the test battery to assess possibility of a conductive component to the HL.

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MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca²⁺ near stereocilia.

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MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca2+ near stereocilia.

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OmicsDI is part of the ELIXIR infrastructure

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MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca²⁺ near stereocilia.