Hair-Cell Mechanotransduction and Cochlear Amplification

LeMasurier, Meredith; Gillespie, Peter G.

doi:10.1016/j.neuron.2005.10.017

Cited by 206 publications

(174 citation statements)

References 117 publications

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“…For instance, in the auditory system, mechanical and molecular properties of the cochlea make it a powerful amplifier (LeMasurier and Gillespie, 2005). In the visual system, the phototransduction cascade insures that a single photon causes a substantial electric response in a photoreceptor, and synaptic circuits in the retina further amplify this signal (Sterling, 2004).…”

Section: The Importance Of a Glomerular Amplifiermentioning

confidence: 99%

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

Jan¹,

Westbrook²

2007

J. Neurosci.

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Sensory systems often respond to rapid stimuli with high frequency and fidelity, as perhaps best exemplified in the auditory system. Fast synaptic responses are fundamental requirements to achieve this task. The importance of speed is less clear in the olfactory system. Moreover, olfactory bulb output mitral cells respond to a single stimulation of the sensory afferents with unusually long EPSPs, lasting several seconds. We examined the temporal characteristics, developmental regulation, and the mechanism generating these responses in mouse olfactory bulb slices. The slow EPSP appeared at postnatal days 10 -11 and was mediated by metabotropic glutamate receptor 1 (mGluR1) and NMDA receptors. mGluR1 contribution was unexpected because its activation usually requires strong, high-frequency stimulation of inputs. However, dendritic release of glutamate from the intraglomerular network caused spillover-mediated recurrent activation of metabotropic glutamate receptors. We suggest that persistent responses in mitral cells amplify the incoming sensory information and, along with asynchronous inputs, drive odor-evoked slow temporal activity in the bulb.

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Section: The Importance Of a Glomerular Amplifiermentioning

confidence: 99%

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

Jan¹,

Westbrook²

2007

J. Neurosci.

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“…Because of these factors, we suggest that PMCA2w/a pumps nearly all Ca 2ϩ that enters outer hair cells into the endolymph, regardless of whether the Ca 2ϩ permeates transduction channels or basolateral Ca 2ϩ channels LeMasurier and Gillespie, 2005), with the net flux depending on the contribution of basolateral Ca 2ϩ channels to Ca 2ϩ dynamics (Kros, 1996). Transcellular Ca 2ϩ flux is well established in transport epithelia and, like in the organ of Corti, is produced by asymmetric distribution of Ca 2ϩ channels, buffers, and pumps (Hoenderop et al, 2005).…”

Section: Segregation Of Pmca Isoforms In the Cochleamentioning

confidence: 99%

“…Although subtectorial Ca 2ϩ elevation remains hypothetical, it makes physiological sense. If outer hair cells are to use Ca 2ϩ -dependent fast adaptation to power amplification (Kennedy et al, 2005;LeMasurier and Gillespie, 2005), the concentration of Ca 2ϩ must be sufficiently high to allow fast adaptation to occur quickly enough. Future experiments must aim at measuring the static concentration of Ca 2ϩ in the subtectorial space and the dynamics of Ca 2ϩ entry and exit in outer hair cells under physiological conditions.…”

Section: Segregation Of Pmca Isoforms In the Cochleamentioning

confidence: 99%

Splice-Site A Choice Targets Plasma-Membrane Ca2+-ATPase Isoform 2 to Hair Bundles

Hill

Williams

LeMasurier

et al. 2006

Journal of Neuroscience

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Localization of mechanotransduction in sensory hair cells to hair bundles requires selective targeting of essential proteins to specific locations. Isoform 2 of the plasma-membrane Ca 2ϩ -ATPase (PMCA2), required for hearing and balance, is found exclusively in hair bundles. We determined the contribution of splicing at the two major splicing sites (A and C) to hair-cell targeting of PMCA2. When PMCA2 isoforms were immunoprecipitated from purified hair bundles of rat utricle, 2w was the only site A variant detected; moreover, immunocytochemistry for 2w in rat vestibular and cochlear tissues indicated that this splice form was located solely in bundles. To demonstrate the necessity of the 2w sequence, we transfected hair cells with PMCA2 containing different variants at splice sites A and C. Although native hair bundles exclusively use the 2a form at splice-site C, epitope-tagged PMCA2w/a and PMCA2w/b were both concentrated in bundles, indicating that site C is not involved in bundle targeting. In contrast, PMCA2z/a was excluded from bundles and was instead targeted to the basolateral plasma membrane. Bundle-specific targeting of PMCA2w/a tagged with green fluorescent protein (GFP) was diminished, suggesting that GFP interfered with splice-site A. Together, these data demonstrate that PMCA2w/a is the hairbundle isoform of PMCA in rat hair cells and that 2w targets PMCA2 to bundles. The 2w sequence is thus the first targeting signal identified for a hair-bundle membrane protein; moreover, the striking distribution of inner-ear PMCA isoforms dictated by selective targeting suggests a critical functional role for segregated pathways of Ca 2ϩ transport.

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“…However, experimental examinations tend to show that the partial closure of the MET channel is accompanied by reduction in tension at the tip-link ͑Stauffer et LeMasurier and Gillespie, 2005͒, which is attributed to elongation of the link between the MET and an unconventional myosin that is responsible for adaptation ͑Gillespie et al, 1993;Holt et al, 2002;Bozovic and Hudspeth, 2003;Martin et al, 2003͒. These observations are puzzling in view of its presumed biological role because such a phase delayed elongation is the property of a damper and not of an amplifier.…”

Section: Introductionmentioning

confidence: 99%

“…In the following, we examine a specific example, which is called a "release model" ͑Stauffer et al, 2005;LeMasurier and Gillespie, 2005͒ for fast adaptation. However, the applicability of the conclusion is not limited to this particular model as it will become clear by the analysis.…”

Section: Introductionmentioning

confidence: 99%

Amplifying effect of a release mechanism for fast adaptation in the hair bundle

Sul

Iwasa

2009

The Journal of the Acoustical Society of America

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A "release" mechanism, which has been experimentally observed as the fast component in the hair bundle's response to mechanical stimulation, appears similar to common mechanical relaxation with a damping effect. This observation is puzzling because such a response is expected to have an amplifying role in the mechanoelectrical transduction process in hair cells. Here it is shown that a release mechanism can indeed have a role in amplification, if it is associated with negative stiffness due to the gating of the mechonoelectric transducer channel.

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Hair-Cell Mechanotransduction and Cochlear Amplification

Cited by 206 publications

References 117 publications

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

Splice-Site A Choice Targets Plasma-Membrane Ca2+-ATPase Isoform 2 to Hair Bundles

Amplifying effect of a release mechanism for fast adaptation in the hair bundle

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