ROCK-dependent and ROCK-independent Control of Cochlear Outer Hair Cell Electromotility (original) (raw)
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Limiting Frequency of the Cochlear Amplifier Based on Electromotility of Outer Hair Cells
Biophysical Journal, 2003
Outer hair cells are the critical element for the sensitivity and sharpness of frequency selectivity of the ear. It is believed that fast motility (electromotility) of these cells is essential for this function. Indeed, force produced by outer hair cells follows their membrane potential very closely at least up to 60 kHz. However, it has been pointed out that the cell's receptor potential is attenuated by a low-pass RC circuit inherent to these cells, with the RC roll-off frequencies significantly lower than their operating frequencies. This would render electromotility ineffective in producing force. To address this issue, we assume that multiple degrees of freedom and vibrational modes due to the complex structure of the organ of Corti provide optimal phases for outer hair cells' force to cancel viscous drag. Our derived frequency limit depends on the drag-capacitance product, not directly on the RC time constant. With a reasonable assumption for the viscous drag, the estimated limit is 10-13 kHz, exceeding the RC corner frequency. Our analysis shows that a fast-activating potassium current can substantially extend the frequency limit by counteracting the capacitive current.
Frontiers in Systems Neuroscience, 2015
Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels.
The Endocochlear Potential Alters Cochlear Micromechanics
Biophysical Journal, 2011
Acoustic stimulation gates mechanically sensitive ion channels in cochlear sensory hair cells. Even in the absence of sound, a fraction of these channels remains open, forming a conductance between hair cells and the adjacent fluid space, scala media. Restoring the lost endogenous polarization of scala media in an in vitro preparation of the whole cochlea depolarizes the hair cell soma. Using both digital laser interferometry and time-resolved confocal imaging, we show that this causes a structural refinement within the organ of Corti that is dependent on the somatic electromotility of the outer hair cells (OHCs). Specifically, the inner part of the reticular lamina up to the second row of OHCs is pulled toward the basilar membrane, whereas the outer part (third row of OHCs and the Hensen's cells) unexpectedly moves in the opposite direction. A similar differentiated response pattern is observed for sound-evoked vibrations: restoration of the endogenous polarization decreases vibrations of the inner part of the reticular lamina and results in up to a 10-fold increase of vibrations of the outer part. We conclude that the endogenous polarization of scala media affects the function of the hearing organ by altering its geometry, mechanical and electrical properties.
The Journal of the Acoustical Society of America, 2005
A computational model is proposed to analyze the active force production in an individual outer hair cell ͑OHC͒ under high-frequency conditions. The model takes into account important biophysical properties of the cell as well as constraints imposed by the surrounding environment. The biophysical properties include the elastic, piezoelectric, and viscous characteristics of the cell wall. The effect of the environment is associated with the stiffness of the constraint and the drag forces acting on the cell due to the interaction with the external and internal viscous fluids. The study concentrated on a combined effect of the transmembrane potential, frequency, and stiffness of the constraints. The effect of the voltage-dependent stiffness of the cell was particularly investigated and it was found to be twofold. First, it results in higher sensitivity and nonlinearity of the OHC active force production in the physiological range. Second, it determines smaller active forces in the hyperpolarization range. The resonant properties of the active force as functions of voltage and the constraint stiffness were also analyzed. The obtained results can be important for a better understanding of the OHC active force production and the contribution of cell electromotility to the cochlear amplification, sensitivity, and nonlinearity.
A mechano-electro-acoustical model for the cochlea: Response to acoustic stimuli
The Journal of the Acoustical Society of America, 2007
A linear, physiologically based, three-dimensional finite element model of the cochlea is developed. The model integrates the electrical, acoustic, and mechanical elements of the cochlea. In particular, the model includes interactions between structures in the organ of Corti ͑OoC͒, piezoelectric relations for outer hair cell ͑OHC͒ motility, hair bundle ͑HB͒ conductance that changes with HB deflection, current flow in the cross section and along the different scalae, and the feed-forward effect. The parameters in the model are based on guinea-pig data as far as possible. The model is vetted using a variety of experimental data on basilar membrane motion and data on voltages and currents in the OoC. Model predictions compare well, qualitatively and quantitatively, with experimental data on basilar membrane frequency response, impulse response, frequency glides, and scala tympani voltage. The close match of the model predictions with experimental data demonstrates the validity of the model for simulating cochlear response to acoustic input and for testing hypotheses of cochlear function. Analysis of the model and its results indicates that OHC somatic motility is capable of powering active amplification in the cochlea. At the same time, the model supports a possible synergistic role for HB motility in cochlear amplification.
Hearing Research, 1998
It is generally believed that the force for the otoacoustic emission (OAE) generation is provided by a mechanism of electromotility, observed in isolated cochlear outer hair cells (OHCs). OHC electromotility is resistant to several ototoxic reagents, it does not depend on ATP hydrolysis, but it can be blocked by specific sulfhydryl reagents: p-chloromercuriphenylsulfonic acid (pCMPS) and p-hydroxymercuriphenylsulfonic acid (pHMPS). We have used these reagents to test whether they also affect OAE. Application of pCMPS and pHMPS on the round window membrane of anesthetized guinea pigs produced a dose-dependent inhibition of the cubic (2F I 3F P ) distortion product OAE (DPOAE). The inhibition developed progressively from high to low frequencies, reflecting the diffusion of the drugs through the cochlear compartment. The effect of pCMPS and pHMPS was different from the effects of furosemide and lethal anoxia, which impair cochlear function but do not block OHC electromotility. pHMPS suppressed DPOAE completely at all sound intensities tested (45^80 dB SPL), whereas furosemide or lethal anoxia caused DPOAE to disappear at lowlevel stimulation (45^60 dB SPL) only. Our results suggest that the OHC electromotility might provide the force for DPOAE generation not only at low, but also at high stimulus intensities. z 1998 Elsevier Science B.V. All rights reserved.
If the electromotility of outer hair cells (OHC) is to reduce the mechanical impedance of the cochlear partition, it must not only deliver a force of sufficient magnitude, but the force must be ex erted at the correct moment in the stimulus cycle. The amplitude and phase of the receptor potential of OHCs in response to direct mechanical stimu lation of the stereocilia bundle were measured for cells isolated from along the entire length of the adult guinea-pig cochlea. Irrespective of their place of origin, the frequency response of the re ceptor potential, for 20-nm stereociliary displace ment per spectral point, was governed by the OHC electrical input impedance measured near the rest ing potential. The response was a low-pass filter with amplitude that decreased by 6 dB/oct and phase that lagged stereocilia displacement by 90°. The comer frequency of the response decreased exponentially from 546 Hz for the shortest OHC (20 |J.m) with an exponential length constant of 25 (im, or equivalently 0.58 oct per 10 (J.m increase of cell length. The tonotopy was achieved by an ex ponential decrease in the total specific conduc tance with increasing cell length, beginning at 66 pS/|im2 for the shortest OHC; the specific capaci tance was constant (2.0 |iF/cm2). The comer frequency was 3-6 oct below the presumed placefrequency.
High-Frequency Force Generation in the Constrained Cochlear Outer Hair Cell: A Model Study
Journal of the Association for Research in Otolaryngology, 2005
Cochlear outer hair cell (OHC) electromotility is believed to be responsible for the sensitivity and frequency selectivity of the mammalian hearing process. Its contribution to hearing is better understood by examining the force generated by the OHC as a feedback to vibration of the basilar membrane (BM). In this study, we examine the effects of the constraints imposed on the OHC and of the surrounding fluids on the cell's high-frequency active force generated under in vitro and in vivo conditions. The OHC is modeled as a viscoelastic and piezoelectric cylindrical shell coupled with viscous intracellular and extracellular fluids, and the constraint is represented by a spring with adjustable stiffness. The solution is obtained in the form of a Fourier series. The model results are consistent with previously reported experiments under both low-and high-frequency conditions. We find that constrained OHCs achieve a much higher corner frequency than free OHCs, depending on the stiffness of the constraint. We analyze cases in which the stiffness of the constraint is similar to that of the BM, reticular lamina, and tectorial membrane, and find that the force per unit transmembrane potential generated by the OHC can be constant up to several tens of kHz. This model, describing the OHC as a local amplifier, can be incorporated into a global cochlear model that considers cochlear hydrodynamics and frequency modulation of the receptor potential, as well as the graded BM stiffness and OHC length.