scholarly journals Calcium entry does not drive fast mechanotransduction adaptation in cochlear hair cells

2019 ◽  
Author(s):  
Giusy A. Caprara ◽  
Andrew A. Mecca ◽  
Yanli Wang ◽  
Anthony J. Ricci ◽  
Anthony W. Peng
Keyword(s):  
Hair Cells ◽  
Time Course ◽  
Dynamic Range ◽  
Calcium Entry ◽  
Hair Bundle ◽  
Adaptation Mechanism ◽  
Calcium Dependent ◽  
Sensory Hair Cells ◽  
Adaptation Response ◽  
Fast Adaptation

AbstractSound detection in auditory sensory hair cells depends on the deflection of the stereocilia hair bundle, which opens mechano-electric transduction (MET) channels. Adaptation is hypothesized to be a critical property of MET that contributes to the wide dynamic range and sharp frequency selectivity of the auditory system. Historically, adaptation was hypothesized to have multiple mechanisms, all of which require calcium entry through MET channels. Our recent work using a stiff probe to displace hair bundles showed that the fastest adaptation mechanism (fast adaptation) does not require calcium entry. Using a fluid-jet stimulus, others obtained data showing only a calcium-dependent fast adaptation response. Here, we identified the source of this discrepancy. Because the hair cell response to a hair bundle stimulus depends critically on the magnitude and time course of the hair bundle deflection, we developed a high-speed imaging technique to quantify this deflection. The fluid jet delivers a force stimulus, and step-like force stimuli lead to a complex time course of hair bundle displacement (mechanical creep), which affects the hair cell’s macroscopic MET current response by masking the time course of the fast adaptation response. Modifying the fluid-jet stimulus to generate a step-like hair bundle displacement produced rapidly adapting currents that did not depend on membrane potential. This indicated that fast adaptation does not depend on calcium entry. We also confirmed the presence of a calcium-dependent slow adaptation process. These results confirm the existence of multiple adaptation processes: a fast adaptation that is not driven by calcium entry and a slower calcium-dependent process.Significance StatementMechanotransduction by sensory hair cells represents a key first step for the sound sensing ability in vertebrates. The sharp frequency tuning and wide dynamic range of sound sensation are hypothesized to require a mechanotransduction adaptation mechanism. For decades, it had been accepted that all adaptation mechanisms require calcium entry into hair cells. However, more recent work indicated that the apparent calcium dependence of the fastest adaptation differs with the method of cochlear hair cell stimulation. Here, we reconcile existing data and show that calcium entry does not drive the fastest adaptation process, independent of the stimulation method.

scholarly journals Decades-old model of slow adaptation in sensory hair cells is not supported in mammals

2020 ◽  
Vol 6 (33) ◽  
pp. eabb4922
Author(s):  
Giusy A. Caprara ◽  
Andrew A. Mecca ◽  
Anthony W. Peng
Keyword(s):  
Hair Cells ◽  
Time Course ◽  
Dynamic Range ◽  
Hair Bundle ◽  
Current Decay ◽  
Vestibular Hair Cells ◽  
Slow Adaptation ◽  
Sensory Hair Cells ◽  
Myosin Motors ◽  
Motor Model

Hair cells detect sound and motion through a mechano-electric transduction (MET) process mediated by tip links connecting shorter stereocilia to adjacent taller stereocilia. Adaptation is a key feature of MET that regulates a cell’s dynamic range and frequency selectivity. A decades-old hypothesis proposes that slow adaptation requires myosin motors to modulate the tip-link position on taller stereocilia. This “motor model” depended on data suggesting that the receptor current decay had a time course similar to that of hair-bundle creep (a continued movement in the direction of a step-like force stimulus). Using cochlear and vestibular hair cells of mice, rats, and gerbils, we assessed how modulating adaptation affected hair-bundle creep. Our results are consistent with slow adaptation requiring myosin motors. However, the hair-bundle creep and slow adaptation were uncorrelated, challenging a critical piece of evidence upholding the motor model. Considering these data, we propose a revised model of hair cell adaptation.

scholarly journals The calcium-activated potassium channels of turtle hair cells.

1995 ◽  
Vol 105 (1) ◽  
pp. 49-72 ◽  
Author(s):  
J J Art ◽  
Y C Wu ◽  
R Fettiplace
Keyword(s):  
Resonant Frequency ◽  
Time Constant ◽  
Hair Cells ◽  
Time Course ◽  
Voltage Dependence ◽  
Bk Channels ◽  
Hair Bundle ◽  
Sk Channels ◽  
Channel Kinetics ◽  
Ca Current

A major factor determining the electrical resonant frequency of turtle cochlear hair cells is the time course of the Ca-activated K current (Art, J. J., and R. Fettiplace. 1987. Journal of Physiology. 385:207-242). We have examined the notion that this time course is dictated by the K channel kinetics by recording single Ca-activated K channels in inside-out patches from isolated cells. A hair cell's resonant frequency was estimated from its known correlation with the dimensions of the hair bundle. All cells possess BK channels with a similar unit conductance of approximately 320 pS but with different mean open times of 0.25-12 ms. The time constant of relaxation of the average single-channel current at -50 mV in 4 microM Ca varied between cells from 0.4 to 13 ms and was correlated with the hair bundle height. The magnitude and voltage dependence of the time constant agree with the expected behavior of the macroscopic K(Ca) current, whose speed may thus be limited by the channel kinetics. All BK channels had similar sensitivities to Ca which produced half-maximal activation for a concentration of approximately 2 microM at +50 mV and 12 microM at -50 mV. We estimate from the voltage dependence of the whole-cell K(Ca) current that the BK channels may be fully activated at -35 mV by a rise in intracellular Ca to 50 microM. BK channels were occasionally observed to switch between slow and fast gating modes which raises the possibility that the range of kinetics of BK channels observed in different hair cells reflects a common channel protein whose kinetics are regulated by an unidentified intracellular factor. Membrane patches also contained 30 pS SK channels which were approximately 5 times more Ca-sensitive than BK channels at -50 mV. The SK channels may underlie the inhibitory synaptic potential produced in hair cells by efferent stimulation.

scholarly journals Mechanical Frequency Tuning by Sensory Hair Cells, the Receptors and Amplifiers of the Inner Ear

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Pascal Martin ◽  
A.J. Hudspeth
Keyword(s):  
Hopf Bifurcation ◽  
Hair Cells ◽  
Force Feedback ◽  
Dynamic Range ◽  
Frequency Tuning ◽  
Hair Bundle ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Waves ◽  
Myosin Motors

We recognize sounds by analyzing their frequency content. Different frequency components evoke distinct mechanical waves that each travel within the hearing organ, or cochlea, to a frequency-specific place. These signals are detected by hair cells, the ear's sensory receptors, in response to vibrations of mechanically sensitive antennas termed hair bundles. An active process enhances the sensitivity, sharpens the frequency tuning, and broadens the dynamic range of hair cells through several mechanisms, including active hair-bundle motility. A dynamic interplay between negative stiffness mediated by ion channels’ gating forces and delayed force feedback owing to myosin motors and channel reclosure by calcium ions brings the hair bundle to the vicinity of an oscillatory instability—a Hopf bifurcation. Operation near a Hopf bifurcation provides nonlinear generic features that are characteristic of hearing. Multiple gradients at molecular, cellular, and supercellular scales tune hair cells to characteristic frequencies that cover our auditory range. Expected final online publication date for the Annual Review of Condensed Matter Physics, Volume 12 is March 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The development of cooperative channels explains the maturation of hair cell’s mechanotransduction

2019 ◽  
Author(s):  
Francesco Gianoli ◽  
Thomas Risler ◽  
Andrei S. Kozlov
Keyword(s):  
Ion Channels ◽  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Hair Bundle ◽  
Mechanical Stimuli ◽  
Biophysical Properties ◽  
Tip Link ◽  
Fast Adaptation ◽  
Kinetics Of

ABSTRACTHearing relies on the conversion of mechanical stimuli into electrical signals. In vertebrates, this process of mechano-electrical transduction (MET) is performed by specialized receptors of the inner ear, the hair cells. Each hair cell is crowned by a hair bundle, a cluster of microvilli that pivot in response to sound vibrations, causing the opening and closing of mechanosensitive ion channels. Mechanical forces are projected onto the channels by molecular springs called tip links. Each tip link is thought to connect to a small number of MET channels that gate cooperatively and operate as a single transduction unit. Pushing the hair bundle in the excitatory direction opens the channels, after which they rapidly reclose in a process called fast adaptation. It has been experimentally observed that the hair cell’s biophysical properties mature gradually during postnatal development: the maximal transduction current increases, sensitivity sharpens, transduction occurs at smaller hair-bundle displacements, and adaptation becomes faster. Similar observations have been reported during tip-link regeneration after acoustic damage. Moreover, when measured at intermediate developmental stages, the kinetics of fast adaptation varies in a given cell depending on the magnitude of the imposed displacement. The mechanisms underlying these seemingly disparate observations have so far remained elusive. Here, we show that these phenomena can all be explained by the progressive addition of MET channels of constant properties, which populate the hair bundle first as isolated entities, then progressively as clusters of more sensitive, cooperative MET channels. As the proposed mechanism relies on the difference in biophysical properties between isolated and clustered channels, this work highlights the importance of cooperative interactions between mechanosensitive ion channels for hearing.SIGNIFICANCEHair cells are the sensory receptors of the inner ear that convert mechanical stimuli into electrical signals transmitted to the brain. Sensitivity to mechanical stimuli and the kinetics of mechanotransduction currents change during hair-cell development. The same trend, albeit on a shorter timescale, is also observed during hair-cell recovery from acoustic trauma. Furthermore, the current kinetics in a given hair cell depends on the stimulus magnitude, and the degree of that dependence varies with development. These phenomena have so far remained unexplained. Here, we show that they can all be reproduced using a single unifying mechanism: the progressive formation of channel pairs, in which individual channels interact through the lipid bilayer and gate cooperatively.

scholarly journals Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells

Development ◽  
2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

scholarly journals Hair-Cell Versus Afferent Adaptation in the Semicircular Canals

2005 ◽  
Vol 93 (1) ◽  
pp. 424-436 ◽  
Author(s):  
R. D. Rabbitt ◽  
R. Boyle ◽  
G. R. Holstein ◽  
S. M. Highstein
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Semicircular Canal ◽  
Time Course ◽  
Dynamic Range ◽  
Cell Voltage ◽  
Frequency Dependent ◽  
Adaptation Time ◽  
Phase Lead ◽  
Flat Gain

The time course and extent of adaptation in semicircular canal hair cells was compared to adaptation in primary afferent neurons for physiological stimuli in vivo to study the origins of the neural code transmitted to the brain. The oyster toadfish, Opsanus tau, was used as the experimental model. Afferent firing-rate adaptation followed a double-exponential time course in response to step cupula displacements. The dominant adaptation time constant varied considerably among afferent fibers and spanned six orders of magnitude for the population (∼1 ms to >1,000 s). For sinusoidal stimuli (0.1–20 Hz), the rapidly adapting afferents exhibited a 90° phase lead and frequency-dependent gain, whereas slowly adapting afferents exhibited a flat gain and no phase lead. Hair-cell voltage and current modulations were similar to the slowly adapting afferents and exhibited a relatively flat gain with very little phase lead over the physiological bandwidth and dynamic range tested. Semicircular canal microphonics also showed responses consistent with the slowly adapting subset of afferents and with hair cells. The relatively broad diversity of afferent adaptation time constants and frequency-dependent discharge modulations relative to hair-cell voltage implicate a subsequent site of adaptation that plays a major role in further shaping the temporal characteristics of semicircular canal afferent neural signals.

Two Components of Transducer Adaptation in Auditory Hair Cells

1999 ◽  
Vol 82 (5) ◽  
pp. 2171-2181 ◽  
Author(s):  
Yuh-Cherng Wu ◽  
A. J. Ricci ◽  
R. Fettiplace
Keyword(s):  
Intracellular Calcium ◽  
Hair Cells ◽  
Time Course ◽  
Similar Time ◽  
Auditory Hair Cells ◽  
Calcium Buffer ◽  
Atpase Inhibitors ◽  
Butanedione Monoxime ◽  
Fast Adaptation ◽  
Dependent Mechanism

Mechanoelectrical transducer currents in turtle auditory hair cells adapted to maintained stimuli via a Ca2+-dependent mechanism characterized by two time constants of ∼1 and 15 ms. The time course of adaptation slowed as the stimulus intensity was raised because of an increased prominence of the second component. The fast component of adaptation had a similar time constant for both positive and negative displacements and was unaffected by the myosin ATPase inhibitors, vanadate and butanedione monoxime. Adaptation was modeled by a scheme in which Ca2+ ions, entering through open transducer channels, bind at two intracellular sites to trigger independent processes leading to channel closure. It was assumed that the second site activates a modulator with 10-fold slower kinetics than the first site. The model was implemented by computing Ca2+diffusion within a single stereocilium, incorporating intracellular calcium buffers and extrusion via a plasma membrane CaATPase. The theoretical results reproduced several features of the experimental responses, including sensitivity to the concentration of external Ca2+ and intracellular calcium buffer and a dependence on the onset speed of the stimulus. The model also generated damped oscillatory transducer responses at a frequency dependent on the rate constant for the fast adaptive process. The properties of fast adaptation make it unlikely to be mediated by a myosin motor, and we suggest that it may result from Ca2+ binding to the transducer channel or a nearby cytoskeletal element.

scholarly journals Multiple PDZ Domain Protein Maintains Patterning of the Apical Cytoskeleton in Sensory Hair Cells

2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

SUMMARYSound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane, and required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia in Mpdz mutants, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

scholarly journals Stereocilia Rootlets: Actin-Based Structures That Are Essential for Structural Stability of the Hair Bundle

2020 ◽  
Vol 21 (1) ◽  
pp. 324 ◽  
Author(s):  
Itallia Pacentine ◽  
Paroma Chatterjee ◽  
Peter G. Barr-Gillespie
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Actin Filaments ◽  
Hair Bundle ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
Associated Proteins ◽  
Unique Manner ◽  
Electrical Impulses ◽  
Mechanical Movement

Sensory hair cells of the inner ear rely on the hair bundle, a cluster of actin-filled stereocilia, to transduce auditory and vestibular stimuli into electrical impulses. Because they are long and thin projections, stereocilia are most prone to damage at the point where they insert into the hair cell’s soma. Moreover, this is the site of stereocilia pivoting, the mechanical movement that induces transduction, which additionally weakens this area mechanically. To bolster this fragile area, hair cells construct a dense core called the rootlet at the base of each stereocilium, which extends down into the actin meshwork of the cuticular plate and firmly anchors the stereocilium. Rootlets are constructed with tightly packed actin filaments that extend from stereocilia actin filaments which are wrapped with TRIOBP; in addition, many other proteins contribute to the rootlet and its associated structures. Rootlets allow stereocilia to sustain innumerable deflections over their lifetimes and exemplify the unique manner in which sensory hair cells exploit actin and its associated proteins to carry out the function of mechanotransduction.

scholarly journals Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in the Inner Ear

2009 ◽  
Vol 1186 ◽  
Author(s):  
Kathryn D Breneman ◽  
Richard D Rabbitt
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Dynamic Range ◽  
Lateral Wall ◽  
Outer Hair Cells ◽  
Hair Bundle ◽  
Relative Significance ◽  
Mechanical Amplification ◽  
As If ◽  
Biological Motors

AbstractThe mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over 100dB dynamic range, and has the exquisite ability to discriminate closely spaced tones even in the presence of noise. This performance is achieved, in part, through active mechanical amplification of vibrations by sensory hair cells within the inner ear. All hair cells are endowed with a bundle of motile microvilli, stereocilia, located at the apical end of the cell, and the more specialized outer hair cells (OHC's) are also endowed with somatic electromotility responsible for changes in cell length in response to perturbations in membrane potential. Both hair bundle and somatic motors are known to feed energy into the mechanical vibrations in the inner ear. The biophysical origin and relative significance of the motors remains a subject of intense research. Several biological motors have been identified in hair cells that might underlie the motor(s), including a cousin of the classical ATP driven actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much too slow to be viable at audio frequencies on a cycle-by-cycle basis. Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane were a piezoelectric material and the hair bundle motor behaves as if the plasma membrane were a flexoelectric material. We propose these observations from a continuum materials perspective are literally true. To examine this idea, we formulated mathematical models of the OHC lateral wall “piezoelectric” motor and the more ubiquitous “flexoelectric” hair bundle motor. Plausible biophysical mechanisms underlying piezo- and flexoelectircity were established. Model predictions were compared extensively to the available data. The models were then applied to study the power conversion efficiency of the motors. Results show that the material properties of the complex membranes in hair cells provide them with the ability to convert electrical power available in the inner ear cochlea into useful mechanical amplification of sound induced vibrations at auditory frequencies. We also examined how hair cell amplification might be controlled by the brain through efferent synaptic contacts on hair cells and found a simple mechanism to tune hearing to signals of interest to the listener by electrical control of these motors.

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