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

Kennedy, Helen J; Evans, Michael G.; Crawford, A. C.; Fettiplace, Robert

doi:10.1523/jneurosci.3808-05.2006

Cited by 82 publications

(68 citation statements)

References 55 publications

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“…Moreover, cochlear amplification is most important at the cochlear base, where the apical shape changes of OHCs are the most pronounced. It has been shown that electromotility forces produced by OHCs along their cell bodies cause deflection of the stereocilia (Kennedy et al, 2006). This mechanism might provide an important route for mechanical feedback contributing to cochlear amplification.…”

Section: How Does the Ajc Reshaping Of Ohcs Assist Their Function In mentioning

confidence: 99%

Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape

et al. 2010

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SUMMARYEpithelial cells acquire diverse shapes relating to their different functions. This is particularly relevant for the cochlear outer hair cells (OHCs), whose apical and basolateral shapes accommodate the functioning of these cells as mechano-electrical and electromechanical transducers, respectively. We uncovered a circumferential shape transition of the apical junctional complex (AJC) of OHCs, which occurs during the early postnatal period in the mouse, prior to hearing onset. Geometric analysis of the OHC apical circumference using immunostaining of the AJC protein ZO1 and Fourier-interpolated contour detection characterizes this transition as a switch from a rounded-hexagon to a non-convex circumference delineating two lateral lobes at the neural side of the cell, with a negative curvature in between. This shape tightly correlates with the 'V'-configuration of the OHC hair bundle, the apical mechanosensitive organelle that converts sound-evoked vibrations into variations in cell membrane potential. The OHC apical circumference remodeling failed or was incomplete in all the mouse mutants affected in hair bundle morphogenesis that we tested. During the normal shape transition, myosin VIIa and myosin II (A and B isoforms) displayed polarized redistributions into and out of the developing lobes, respectively, while Shroom2 and F-actin transiently accumulated in the lobes. Defects in these redistributions were observed in the mutants, paralleling their apical circumference abnormalities. Our results point to a pivotal role for actomyosin cytoskeleton tensions in the reshaping of the OHC apical circumference. We propose that this remodeling contributes to optimize the mechanical coupling between the basal and apical poles of mature OHCs.

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Section: How Does the Ajc Reshaping Of Ohcs Assist Their Function In mentioning

confidence: 99%

Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape

et al. 2010

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“…The hair bundle may also provide active force pro-duction (Kennedy et al, 2005;Chan and Hudspeth, 2005a,b), which gives some amplification in the absence of somatic motility in prestin knock-out mouse (Liberman et al, 2004). Bundle amplification and somatic motility may potentially interact (Kennedy et al, 2006); thus, it is important to determine whether there is ultrastructural evidence for connections between the bundle and the lateral wall.…”

Section: Introductionmentioning

confidence: 99%

The Dimensions and Composition of Stereociliary Rootlets in Mammalian Cochlear Hair Cells: Comparison between High- and Low-Frequency Cells and Evidence for a Connection to the Lateral Membrane

Furness

Mahendrasingam²,

Ohashi³

et al. 2008

Journal of Neuroscience

124

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The sensory bundle of vertebrate cochlear hair cells consists of actin-containing stereocilia that are thought to bend at their ankle during mechanical stimulation. Stereocilia have dense rootlets that extend through the ankle region to anchor them into the cuticular plate. Because this region may be important in bundle stiffness and durability during prolonged stimulation at high frequencies, we investigated the structure and dimensions of rootlets relative to the stereocilia in apical (low-frequency) and basal (high-frequency) regions of rodent cochleae using light and electron microscopy. Their composition was investigated using postembedding immunogold labeling of tropomyosin, spectrin, ␤-actin, ␥-actin, espin, and prestin. The rootlets have a thick central core that widens at the ankle, and are embedded in a filamentous meshwork in the cuticular plate. Within a particular frequency region, rootlet length correlates with stereociliary height but between regions it changes disproportionately; apical stereocilia are, thus, approximately twice the height of basal stereocilia in equivalent rows, but rootlet lengths increase much less. Some rootlets contact the tight junctions that underlie the ends of the bundle. Rootlets contain spectrin, tropomyosin, and ␤-and ␥-actin, but espin was not detected; spectrin is also evident near the apical and junctional membranes, whereas prestin is confined to the basolateral membrane below the junctions. These data suggest that rootlets strengthen the ankle region to provide durability and may contact with the lateral wall either to give additional anchoring of the stereocilia or to provide a route for interactions between the bundle and the lateral wall.

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“…Sulfate reduces somatic electromotility [6] acting directly on prestin [10]. Replacement of intracellular chloride with sulfate, in our experiment, did not appear to influence the efficacy of the extracellular applied 9AC.…”

Section: Discussionmentioning

confidence: 38%

Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

Harasztosi¹,

Gummer²,

Shera³

et al. 2011

AIP Conference Proceedings

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Abstract. The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

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

Cited by 82 publications

References 55 publications

Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape

Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape

The Dimensions and Composition of Stereociliary Rootlets in Mammalian Cochlear Hair Cells: Comparison between High- and Low-Frequency Cells and Evidence for a Connection to the Lateral Membrane

Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

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