Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging

Beurg, Maryline; Fettiplace, Robert; Nam, Jong-Hoon; Ricci, Anthony J.

doi:10.1038/nn.2295

Cited by 399 publications

(417 citation statements)

References 22 publications

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“…Our results demonstrate that gating of the transduction channels provides a major contribution to hair-bundle friction. It is striking that a few tens of ion channels (19,20) can have a significant effect on friction of a structure as large as the micrometer-sized hair-cell bundle. If channel friction resulted simply from viscous drag associated with conformational changes of the channels moving in a fluid, we would estimate a friction coefficient ξ H that is nearly four orders of magnitude lower than the value λ C ≅ 340 nN·s·m −1 measured here at low bundle velocity (SI Appendix, section 4).…”

Section: Discussionmentioning

confidence: 99%

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

Bormuth

Barral

Joanny

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell's characteristic frequency of responsiveness.mechanosensitive channels | protein friction | hair-bundle mechanosensitivity | cell mechanics | auditory system S ound evokes vibrations in the inner ear that are detected by sensory hair cells. Mechanosensitivity stems from mechanical activation of ion channels by tension changes in tip links that interconnect neighboring stereocilia of the hair-cell bundle (1). The acute sensitivity and sharp frequency selectivity of auditory detection rely on efficient transmission of the energy derived from the acoustic stimulus to the apparatus that mediates mechanoelectrical transduction. However, at least three sources of friction threaten to dissipate the energy of the vibrating hair bundle. First, viscous drag by the surrounding fluid provides a minimum source of damping (2, 3). Second, viscoelasticity of the tip links, or of proteins in series with these links, may result in additional dissipation during hair-bundle deflections (4). Third, an intrinsic source of friction-called "channel friction" in the following-is related to thermal fluctuations of the transduction channels between their open and closed states (5). The fluctuation-dissipation theorem dictates that this source of mechanical noise be related to friction forces on the hair bundle.To circumvent the fundamental challenge posed by friction, hair cells mobilize internal ...

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Section: Discussionmentioning

confidence: 99%

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

Bormuth

Barral

Joanny

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…This process depends on the opening of mechanoelectrical transducer (MET) channels located at the tips of the shorter of pairs of adjacent stereocilia (1), which are specialized microvilli-like structures that form the hair bundles that project from the upper surface of hair cells (2,3). Deflection of hair bundles in the excitatory direction (i.e., toward the taller stereocilia) stretches specialized linkages, the tip-links, present between adjacent stereocilia (3)(4)(5), opening the MET channels.…”

mentioning

confidence: 99%

Calcium entry into stereocilia drives adaptation of the mechanoelectrical transducer current of mammalian cochlear hair cells

Corns

Johnson

Kros

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

109

186

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Mechanotransduction in the auditory and vestibular systems depends on mechanosensitive ion channels in the stereociliary bundles that project from the apical surface of the sensory hair cells. In lower vertebrates, when the mechanoelectrical transducer (MET) channels are opened by movement of the bundle in the excitatory direction, Ca 2+ entry through the open MET channels causes adaptation, rapidly reducing their open probability and resetting their operating range. It remains uncertain whether such Ca 2+ -dependent adaptation is also present in mammalian hair cells. Hair bundles of both outer and inner hair cells from mice were deflected by using sinewave or step mechanical stimuli applied using a piezo-driven fluid jet. We found that when cochlear hair cells were depolarized near the Ca 2+ reversal potential or their hair bundles were exposed to the in vivo endolymphatic Ca 2+ concentration (40 μM), all manifestations of adaptation, including the rapid decline of the MET current and the reduction of the available resting MET current, were abolished. MET channel adaptation was also reduced or removed when the intracellular Ca 2+ buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) was increased from a concentration of 0.1 to 10 mM. The findings show that MET current adaptation in mouse auditory hair cells is modulated similarly by extracellular Ca 2+ , intracellular Ca 2+ buffering, and membrane potential, by their common effect on intracellular free Ca 2+ .H earing and balance depend on the transduction of mechanical stimuli into electrical signals. This process depends on the opening of mechanoelectrical transducer (MET) channels located at the tips of the shorter of pairs of adjacent stereocilia (1), which are specialized microvilli-like structures that form the hair bundles that project from the upper surface of hair cells (2,3). Deflection of hair bundles in the excitatory direction (i.e., toward the taller stereocilia) stretches specialized linkages, the tip-links, present between adjacent stereocilia (3-5), opening the MET channels. In hair cells from lower vertebrates, open MET channels reclose during constant stimuli via an initial fast adaptation mechanism followed by a much slower, myosin-based motor process, both of which are driven by Ca 2+ entry through the channel itself (6-13). In mammalian auditory hair cells, MET current adaptation seems to be mainly driven by the fast mechanism (14-16), although the exact process by which it occurs is still largely unknown. The submillisecond speed associated with the adaptation kinetics of the MET channels in rat and mouse cochlear hair cells (17,18) indicates that Ca 2+ , to cause adaptation, has to interact directly with a binding site on the channel or via an accessory protein (16). However, a recent investigation on rat auditory hair cells has challenged the view that Ca 2+ entry is required for fast adaptation, and instead proposed an as-yetundefined mechanism involving a Ca 2+ -independent reduction in the viscoelastic force of ele...

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“…Cochlear hair bundles contain three rows of actin-filled stereocilia of increasing heights, forming a regular staircase pattern. This architecture ensures the effective gating of mechanoelectrical transduction (MET) channels located at the tips of the stereocilia in the short and middle rows (Beurg et al, 2009). The cochlea contains two types of hair cells, the inner hair cells (IHCs) and the outer hair cells (OHCs), with distinct "U"-like and "V"-like hair bundle shapes, respectively.…”

Section: Introductionmentioning

confidence: 99%

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Lelli¹,

Michel²,

Monvel³

et al. 2016

J Gen Physiol

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Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging

Cited by 399 publications

References 22 publications

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

Calcium entry into stereocilia drives adaptation of the mechanoelectrical transducer current of mammalian cochlear hair cells

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

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