Effects of Salicylate on Shape, Electromotility and Membrane Characteristics of Isolated Outer Hair Cells from Guinea Pig Cochlea

Shehata, W. E.; Brownell, William E.; Dieler, R.

doi:10.3109/00016489109138403

Cited by 180 publications

(124 citation statements)

References 22 publications

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“…This inhibition would reduce both constructive and destructive interference caused by intracochlear reflections of the evoked OAE. Similar upward threshold shifts and reductions in fine structure depth have been observed following noise exposure (Furst et al 1992) and sustained (∼3 days) consumption of aspirin (Long and Tubis 1988a, b), which is known to inhibit OHC function (Shehata et al 1991;Dieler et al 1991).…”

Section: Interactions Among Cochlear Gain Soaes and Thresholdsmentioning

confidence: 55%

Effects of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions and Hearing Threshold Fine Structure

Dewey

Lee

Dhar

2014

JARO

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Medial olivocochlear (MOC) influence on cochlear mechanics can be noninvasively, albeit indirectly, explored via the effects of contralateral acoustic stimulation (CAS) on otoacoustic emissions. CASmediated effects are particularly pronounced for spontaneous otoacoustic emissions (SOAEs), which are typically reduced in amplitude and shifted upward in frequency by CAS. We investigated whether similar frequency shifts and magnitude reductions were observed behaviorally in the fine structure of puretone hearing thresholds, a phenomenon thought to share a common underlying mechanism with SOAEs. In normal-hearing listeners, fine-resolution thresholds were obtained over a narrow frequency range centered on the frequency of an SOAE, both in the absence and presence of 60-dB SPL broadband CAS. While CAS shifted threshold fine structure patterns and SOAEs upward in frequency by a comparable amount, little reduction in the presence or depth of fine structure was observed at frequencies near those of SOAEs. In fact, CAS typically improved thresholds, particularly at threshold minima, and increased fine structure depth when reductions in the amplitude of the associated SOAE were less than 10 dB. Additional measurements made at frequencies distant from SOAEs, or near SOAEs that were more dramatically reduced in amplitude by the CAS, revealed that CAS tended to elevate thresholds and reduce threshold fine structure depth. The results suggest that threshold fine structure is sensitive to MOC-mediated changes in cochlear gain, but that SOAEs complicate the interpretation of threshold measurements at nearby frequencies, perhaps due to masking or other interference effects. Both threshold fine structure and SOAEs may be significant sources of intersubject and intrasubject variability in psychoacoustic investigations of MOC function.

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Section: Interactions Among Cochlear Gain Soaes and Thresholdsmentioning

confidence: 55%

Effects of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions and Hearing Threshold Fine Structure

Dewey

Lee

Dhar

2014

JARO

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“…All cells studied displayed mechanotransduction, and the displacement was always in the positive direction with amplitude of several tens of nanometers. Two lines of evidence strongly argue that the movements were partly driven by somatic contractions thought to be mediated by prestin: (1) a concomitant motion of the hair bundle of the cell adjacent to the one being polarized; (2) at least a 70% reduction in the displacement amplitude by Na salicylate, a blocker of somatic contractility (Shehata et al, 1991;Kakehata and Santos-Sacchi, 1996). Salicylate is not a completely specific agent to use on auditory hair cells because it has been has found to elevate the sound threshold at the characteristic frequency of pigeon auditory nerve fibers (Shehata-Dieler et al, 1994) and to suppress otoacoustic emissions in lizards (Stewart and Hudspeth, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…OHC motility and the associated nonlinear capacitance are known to be blocked by Na salicylate (Shehata et al, 1991) with half-inhibition (K I ) in the millimolar range [K I of 4 mM (Tunstall et al, 1995); K I of 1.6 mM (Kakehata and SantosSacchi 1996)]. External perfusion with 10 mM Na salicylate produced a reduction in the hair bundle displacement and abolition of the nonlinear capacitance seen in the current transients at the start and end of the voltage step (Fig.…”

Section: Contribution Of the Somatic Motor To Hair Bundle Movementsmentioning

confidence: 99%

Depolarization of Cochlear Outer Hair Cells Evokes Active Hair Bundle Motion by Two Mechanisms

et al. 2006

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There is current debate about the origin of mechanical amplification whereby outer hair cells generate force to augment the sensitivity and frequency selectivity of the mammalian cochlea. To distinguish contributions to force production from the mechanotransducer (MET) channels and somatic motility, we have measured hair bundle motion during depolarization of individual outer hair cells in isolated rat cochleas. Depolarization evoked rapid positive bundle deflections that were reduced by perfusion with the MET channel blocker dihydrostreptomycin, with no effect on the nonlinear capacitance that is a manifestation of prestin-driven somatic motility. However, the movements were also diminished by Na salicylate and depended on the intracellular anion, properties implying involvement of the prestin motor. Furthermore, depolarization of one outer hair cell caused motion of neighboring hair bundles, indicating overall motion of the reticular lamina. Depolarization of solitary outer hair cells caused cell-length changes whose voltage-activation range depended on the intracellular anion but were insensitive to dihydrostreptomycin. These results imply that both the MET channels and the somatic motor participate in hair bundle motion evoked by depolarization. It is conceivable that the two processes can interact, a signal from the MET channels being capable of modulating the activity of the prestin motor.

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“…Using the Prestin Inhibitor, Salicylate, to Unravel the Steps in Prestin Operation-Salicylate is an inhibitor of OHC electromotility (7,17,18), which is thought to compete with anions such as chloride for the anion-binding site on prestin (19). Fig.…”

Section: Twomentioning

confidence: 99%

Evidence That Prestin Has at Least Two Voltage-dependent Steps

Homma

Dallos

2011

Journal of Biological Chemistry

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Prestin is a voltage-dependent membrane-spanning motor protein that confers electromotility on mammalian cochlear outer hair cells, which is essential for normal hearing of mammals. Voltage-induced charge movement in the prestin molecule is converted into mechanical work; however, little is known about the molecular mechanism of this process. For understanding the electromechanical coupling mechanism of prestin, we simultaneously measured voltage-dependent charge movement and electromotility under conditions in which the magnitudes of both charge movement and electromotility are gradually manipulated by the prestin inhibitor, salicylate. We show that the observed relationships of the charge movement and the physical displacement (q-d relations) are well represented by a three-state Boltzmann model but not by a two-state model or its previously proposed variant. Here, we suggest a molecular mechanism of prestin with at least two voltage-dependent conformational transition steps having distinct electromechanical coupling efficiencies.Electromotility (1) of mammalian cochlear outer hair cells (OHCs) 2 is a rapid voltage-induced force-generating cell length change that is indispensable for the frequency selectivity and sensitivity of mammalian hearing (2). The membranebased motor protein, prestin, which is a member of the solute carrier 26 anion transporter family (3), is known to be responsible for generating electromotility (4). Accompanying OHC electromotility, charge movement in the lateral membrane of the cell is observed. This charge movement is manifested in the bell-shaped voltage-dependent cell membrane capacitance, which is often referred to as nonlinear capacitance (NLC) (5, 6)).The question of how prestin functions as a membranebased molecular motor has received a great deal of attention; however, even some fundamental issues are still obscure. To understand the mode of operation of the molecule, the relationship between charge movement, which initiates conformational change, and motor function needs to be quantified. However, only minimal attempts have been made to this effect (6, 7). Under normal operating circumstances NLC data are usually well explained by the simple two-state Boltzmann model with an apparent valency of charge of less than unity. Interesting theoretical work suggested that three-or higher-state models might provide superior description of the process (8, 9). In some work three-state fits were dictated by the data (10). To explain some properties of NLC at extreme membrane voltages, a modified two-state model has also been proposed (11). However, those models have not been subjected to rigorous examination as to their generality under various experimental conditions. It is one purpose of the present work to provide such an examination. We find that a Boltzmann model with at least two voltage-dependent steps is required for explaining prestin function.Since the discovery of prestin, assessments of effects of mutations and drugs on its function have become readily feasible using heter...

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Effects of Salicylate on Shape, Electromotility and Membrane Characteristics of Isolated Outer Hair Cells from Guinea Pig Cochlea

Cited by 180 publications

References 22 publications

Effects of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions and Hearing Threshold Fine Structure

Effects of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions and Hearing Threshold Fine Structure

Depolarization of Cochlear Outer Hair Cells Evokes Active Hair Bundle Motion by Two Mechanisms

Evidence That Prestin Has at Least Two Voltage-dependent Steps

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