Outer Hair Cell Somatic Motility Research Articles

An expanding mechanical role for the tiny mammalian endolymphatic duct: 1. Modification of Békésy model is specifically needed to cope with ambient pressure variation—with weather, altitude or ocean depth

von Békésy’s pioneering work and two-chamber model with basilar membrane (BM) separating the perilymph chambers was a first-pass assumption which worked to explain basic frequency-band analysis. Yet it did not cover psychoacoustical phenomena. Nor did it cover the repeated demonstrations by this author of baseline displacements of the BM, nor mysterious changes in the volume of the tiny endolymphatic duct—even in human ears with normal thresholds. Since 2009 the duct has been shown to possess all the necessary characteristics of a pressure vessel, viz., it is lined with aquaporins and tight junctions while the cells of the stria vascularis maintain a strict osmotic gradient. We submit that such evolutionary change was necessary because ambient pressure changes are too large to be corrected by passive equalization and need to be actively eliminated to preserve hearing sensitivity. Any theory must cover marine mammals which have adapted to ocean pressures measured in megapascals. In this case, infrasound is modelled as a varying pressure pedestal which must be cancelled. This video presentation covers one possible mechanical configuration for how such a cancelation might be achieved—a hypothesized feedback control system utilizing outer hair cell somatic motility plus our previously-modelled otolith-based pressure transducer.

A study of active artificial hair cell models inspired by outer hair cell somatic motility

The cochlea displays an important, nonlinear amplification of sound-induced oscillations. In mammals, this amplification is largely powered by the somatic motility of the outer hair cells. The resulting cochlear amplifier has three important characteristics useful for hearing: an amplification of responses from low sound pressures, an improvement in frequency selectivity, and an ability to transduce a broad range of sound pressure levels. These useful features can be incorporated into designs for active artificial hair cells, bio-inspired sensors for use as microphones, accelerometers, or other dynamic sensors. The sensor consists of a cantilever beam with piezoelectric actuators. A feedback controller applies a voltage to the actuators to mimic the outer hair cells’ somatic motility. This article describes three control laws for an active artificial hair cell inspired by models of the outer hair cells’ somatic motility. The first control law is based on a phenomenological model of the cochlea while the second and third models incorporate physiological aspects of the biological cochlea to further improve sensor performance. Simulations show that these models qualitatively reproduce the key aspects of the mammalian cochlea, namely, amplification of oscillations from weak stimuli, higher quality factors, and a wider input dynamic range.

Nonlinear dynamics of the organ of Corti, modeling both outer hair cell somatic motility and hair bundle motility

One of the principal questions in the cochlea biophysics is the determination of relative contributions of the two active processes, OHC somatic motility and HB motility, to the mechanics of the cochlea. Because of the difficulty of eliminating one mechanism without affecting the other, an unambiguous in vivo measurement differentiating their effects remains elusive. Theoretical models, therefore, have been used as one way to examine the contributions of the two active mechanisms to cochlear mechanics. In this paper, we use a physiologically based model of the mammalian organ of Corti to study the hearing active process and the relative contributions of these active forces. This local model integrates the electrical, acoustic, and mechanical elements of a cross section of the cochlea. The nonlinear dynamics of this model are studied with a special emphasis on the regions of stability and the amplification of the mechanical response arising from the active processes. [Work supported by NIH-NIDCD R01-04084 and NIH NIDCD-T32-000011.]

Membrane Thickness Sensitivity of Prestin Orthologs: The Evolution of a Piezoelectric Protein

How proteins evolve new functionality is an important question in biology; prestin (SLC26A5) is a case in point. Prestin drives outer hair cell somatic motility and amplifies mechanical vibrations in the mammalian cochlea. The motility of mammalian prestin is analogous to piezoelectricity, in which charge transfer is coupled to changes in membrane area occupied by the protein. Intriguingly, nonmammalian prestin orthologs function as anion exchangers but are apparently nonmotile. We previously found that mammalian prestin is sensitive to membrane thickness, suggesting that prestin's extended conformation has a thinner hydrophobic height in the lipid bilayer. Because prestin-based motility is a mammalian specialization, we initially hypothesized that nonmotile prestin orthologs, while functioning as anion transporters, should be much less sensitive to membrane thickness. We found the exact opposite to be true. Chicken prestin was the most sensitive to thickness changes, displaying the largest shift in voltage dependence. Platypus prestin displayed an intermediate response to membrane thickness and gerbil prestin was the least sensitive. To explain these observations, we present a theory where force production, rather than displacement, was selected for the evolution of prestin as a piezoelectric membrane motor.

Prediction of the Effect of Adaptation and Active HB Mechanics on Prestin-Based Amplification Using a Macroscopic Model of the Cochlea

The identity of the mammalian cochlear amplifier is a highly debated issue in auditory mechanics. Two different active processes could underlie cochlear amplification: somatic motility and hair bundle (HB) motility. We use a mathematical model of the cochlea to investigate the role of somatic motility and active HB dynamics. The HB is modeled by a nonlinear six-state channel with a calcium binding event responsible for fast adaptation of the transduction and active HB force generation. The dynamics of the HB are linearized for small harmonic perturbation around the operating point and implemented in a macroscopic model of the cochlea that includes feedback from outer hair cell somatic motility. The simulations of the response of the cochlea to low intensity acoustic stimulation show that somatic motility and not HB motility can modulate the BM motion. However the effect of fast adaptation on the transduction channel is a reduction of the sensitivity of the channel to HB deflection that could serve to control the energy delivered by somatic motility and thereby the gain of the BM to low intensity acoustic stimulation. Funded by NIH grant NIH-NIDCD R01-04084.

Streptomycin and gentamicin have no immediate effect on outer hair cell electromotility

The cochlear outer hair cell (OHC), which plays a crucial role in mammalian hearing through its unique voltage-dependent motility, has been established as a primary target of the ototoxicity of aminoglycoside antibiotics. These polycationic drugs are also known to block a wide variety of ion channels, purinergic ionotropic channels, and nicotinic ACh receptors in hair cells in vitro. The OHC motor protein, prestin, is a voltage-sensitive transmembrane protein containing several negatively charged residues on both intra- and extracellular surface. The acidic sites may be susceptible to polycationic-charged aminoglycoside binding, which may result in disruption of motility. We attempted to examine whether aminoglycosides such as streptomycin and gentamicin could affect OHC motility and its electrical signature, the nonlinear capacitance (NLC) in adult gerbil OHCs. Somatic motility and NLC were measured under the whole-cell voltage-clamp mode. Streptomycin and gentamicin were applied extracellularly or intracellularly. Results show that streptomycin and gentamicin did not change either the magnitude of motility or the NLC. Theses results suggest that, although streptomycin and gentamicin can block mechanotransduction channels as well as ACh receptors in hair cells, they have no direct affect on OHC somatic motility.

Evidence for Outer Hair Cell Driven Oscillatory Fluid Flow in the Tunnel of Corti

Outer hair cell (OHC) somatic motility plays a key role in mammalian cochlear frequency selectivity and hearing sensitivity, but the mechanism of cochlear amplification is not well understood and remains a matter of controversy. We have visualized and quantified the effects of electrically evoked OHC somatic motility within the gerbil organ of Corti using an excised cochlear preparation. We found that OHC motility induces oscillatory motion of the medial olivocochlear fibers where they cross the tunnel of Corti (ToC) in their course to innervate the OHCs. We show that this motion is present at physiologically relevant frequencies and remains at locations distal to the OHC excitation point. We interpret this fiber motion to be the result of oscillatory fluid flow in the ToC. We show, using a simple one-dimensional hydromechanical model of the ToC, that a fluid wave within the tunnel can travel without significant attenuation for distances larger than the wavelength of the cochlear traveling wave at its peak. This ToC fluid wave could interact with the cochlear traveling wave to amplify the motion of the basilar membrane. The ToC wave could also provide longitudinal coupling between adjacent sections of the basilar membrane, and such coupling may be critical for cochlear amplification.

A mechano-electro-acoustical model for the cochlea: Response to acoustic stimuli

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 (OoC), piezoelectric relations for outer hair cell (OHC) motility, hair bundle (HB) 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.

Imaging Electrically Evoked Micromechanical Motion within the Organ of Corti of the Excised Gerbil Cochlea

The outer hair cell (OHC) of the mammalian inner ear exhibits an unusual form of somatic motility that can follow membrane-potential changes at acoustic frequencies. The cellular forces that produce this motility are believed to amplify the motion of the cochlear partition, thereby playing a key role in increasing hearing sensitivity. To better understand the role of OHC somatic motility in cochlear micromechanics, we developed an excised cochlea preparation to visualize simultaneously the electrically-evoked motion of hundreds of cells within the organ of Corti (OC). The motion was captured using stroboscopic video microscopy and quantified using cross-correlation techniques. The OC motion at ∼2–6 octaves below the characteristic frequency of the region was complex: OHC, Deiter’s cell, and Hensen’s cell motion were hundreds of times larger than the tectorial membrane, reticular lamina (RL), and pillar cell motion; the inner rows of OHCs moved antiphasic to the outer row; OHCs pivoted about the RL; and Hensen’s cells followed the motion of the outer row of OHCs. Our results suggest that the effective stimulus to the inner hair cell hair bundles results not from a simple OC lever action, as assumed by classical models, but by a complex internal motion coupled to the RL.

Otoacoustic emissions without somatic motility: can stereocilia mechanics drive the mammalian cochlea?

Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by approximately 50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic (CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear.

What drives mechanical amplification in the mammalian cochlea?

The recent report by Peter Dallos and colleagues of the gene and protein responsible for outer hair cell somatic motility (Zheng, Shen, He, Long, Madison, & Dallos, 2000), and the work of James Hudspeth and colleagues demonstrating that vestibular stereocilia are capable of providing power that may boost the vibration of structures within the inner ear (Martin & Hudspeth, 1999), presents the tantalizing possibility that we may not be far away from answering the question what drives mechanical amplification in the mammalian cochlea? This article reviews the evidence for and against each of somatic motility as the motor, and a motor in the hair cell bundle, producing cochlear mechanical amplification. We consider three models based on somatic motility as the motor and two based on a motor in the hair cell bundle. Available evidence supports a hair cell bundle motor in nonmammals but the upper frequency limit of mammalian hearing in general exceeds that of nonmammals, in many cases by an order of magnitude or more. Only time will tell whether an evolutionary dichotomy exists (Manley, Kirk, Köppl, & Yates, 2001).