The how and why of identifying the hair cell mechano-electrical transduction channel

Effertz, Thomas; Scharr, Alexandra L.; Ricci, Anthony J.

doi:10.1007/s00424-014-1606-z

Cited by 17 publications

(14 citation statements)

References 113 publications

(188 reference statements)

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“…Recently the putative TMC1 channel, which is mutated in hereditary forms of deafness, and its homologue TMC2 have been proposed as the molecular correlates of the hair cell transduction channel (Kawashima et al, 2011). However, their identity as the transduction channel is still a matter of debate (Effertz et al, 2015). A major recent advancement in the study of mechanosensation was the molecular identification of piezo1, the ion channel that underlies the currents induced by mechanical stimulation of dorsal root ganglion neurons and N2A cells, and its close homologue, piezo2, which also mediates mechanosensitive currents in heterologous expression systems (Coste et al, 2010).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…However, their function as mechanotransducers in mammals is not clearly established (Geffeney and Goodman, 2012). One of the most sought-for mechanosensitive ion channels is the transduction channel of the inner ear hair cells that transduces nanometer hair cell cilia deflection in electrical hair cell activity which underlies sound perception (Effertz et al, 2015). Recently the putative TMC1 channel, which is mutated in hereditary forms of deafness, and its homologue TMC2 have been proposed as the molecular correlates of the hair cell transduction channel (Kawashima et al, 2011).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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The biophysics of piezo1 and piezo2 mechanosensitive channels

Soattin

Fiore

Gavazzo

et al. 2016

Biophysical Chemistry

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

The biophysics of piezo1 and piezo2 mechanosensitive channels

Soattin

Fiore

Gavazzo

et al. 2016

Biophysical Chemistry

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“…In Tmc1:Tmc2 double mutants, or after destruction of the tip links, the normal MT current is lost, only to be replaced by a mechanically sensitive current evoked by stimuli of reverse polarity (10)(11)(12). Whether the channels underlying these reverse-polarity currents are the same as those in unperturbed cells is uncertain (2,13). Two questions arise about them: where are they located on the hair cell, and do they only appear under pathological circumstances, as in destruction of tip links or mutations causing loss of transduction?…”

mentioning

confidence: 99%

Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells

Beurg

Goldring

Ricci

et al. 2016

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

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Cochlear hair cells normally detect positive deflections of their hair bundles, rotating toward their tallest edge, which opens mechanotransducer (MT) channels by increased tension in interciliary tip links. After tip-link destruction, the normal polarity of MT current is replaced by a mechanically sensitive current evoked by negative bundle deflections. The "reverse-polarity" current was investigated in cochlear hair cells after tip-link destruction with BAPTA, in transmembrane channel-like protein isoforms 1/2 (Tmc1:Tmc2) double mutants, and during perinatal development. This current is a natural adjunct of embryonic development, present in all wild-type hair cells but declining after birth with emergence of the normal-polarity current. Evidence indicated the reverse-polarity current seen developmentally was a manifestation of the same ion channel as that evident under abnormal conditions in Tmc mutants or after tip-link destruction. In all cases, sinusoidal fluid-jet stimuli from different orientations suggested the underlying channels were opened not directly by deflections of the hair bundle but by deformation of the apical plasma membrane. Cell-attached patch recording on the hair-cell apical membrane revealed, after BAPTA treatment or during perinatal development, 90-pS stretch-activated cation channels that could be blocked by Ca 2+ and by FM1-43. High-speed Ca 2+ imaging, using swept-field confocal microscopy, showed the Ca 2+ influx through the reverse-polarity channels was not localized to the hair bundle, but distributed across the apical plasma membrane. These reverse-polarity channels, which we propose to be renamed "unconventional" mechanically sensitive channels, have some properties similar to the normal MT channels, but the relationship between the two types is still not well defined.hair cells | mechanotransducer channels | calcium imaging | cochlea | transmembrane channel-like protein I on channels sensitive to mechanical deformation of the cell membrane are widely distributed in vertebrates and are integral to the function of specialized mechanoreceptors, such as those in the sensory neurons of the skin, vasculature, or inner ear. The molecular structure of these mechanically gated channels has been the subject of much recent research and speculation (1-4) because they are the last category of vertebrate ion-channel (after voltage-gated and ligand-activated channels) evading characterization. Although success was achieved by assigning piezo2 as a transduction channel in many cutaneous touch receptors (3), uncertainty persists about the composition of the mechanotransducer (MT) channel in hair cells of the inner ear (2, 4). There, the MT channels reside in the stereociliary (hair) bundle, where they are activated by deflections of the bundle toward the taller edge of the staircase, and so increasing tension in the oblique extracellular tip links connecting adjacent stereocilia. Transmembrane channel-like protein isoforms 1 and 2, TMC1 and TMC2 (5), have been suggested as candidates for the ha...

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“…Especially if it turns out that the TMC proteins are not pore forming subunits, other proteins or protein complexes have to be considered. In conclusion, more investigation is needed and existing theories have to be validated to completely understand the structure and working mechansism of the mechanotransducer channel in stereocilia of hair cells .…”

Section: Hearingmentioning

confidence: 99%

Sensor Devices Inspired by the Five Senses: A Review

Svechtarova¹,

Buzzacchera²,

Toebes³

et al. 2016

Electroanalysis

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1IntroductionWearable sensor technology is at the forefront of popular media and at the same time is the subject of intense activity in the scientific world. Thes cientificallyd rivenq uantified self focuseso nc ollecting data on the human state to gather information to improve quality of life,t he more extreme end of the spectrume ncompasses biohacktivism and the post-humanist grinderm ovementa dvocating the use of DIY implants to augment the human body to at ranshuman state. [1][2][3][4][5][6][7][8][9][10][11][12][13].T he focus of the current state of the mainstreama rt rests in augmenting the body with ar ange of relatively simplistica rtificial sensors such as temperature,a ccelerometers for posture and motion, electrocardiology,a nd basic chemical sensors sucha sg lucose monitors.I nf act the body is already at reasure-trove of informationa nd integrated sensor systems that are waitingt ob et apped by the next generation of wearable sensor devices.T he human brain like am odern computer or smartphone,c an process thousands of signals from various inputs in an instant. These primary senses were first definedb yA ristotle in Sense and Sensebilia [14] however it was rather Plato in Theateus that first postulated to humansa nd animals being an etwork of "perceptions" when Socratess tatedt hat "The nameless ones are unlimited in number, but those which have been given names are extremely numerous" [15].J ust as am odern smartphone incorporates multiple sensors such as gyroscope, accelerometer, magnetometer and barometers in concert to accurately determine,a ggregate and presents implified locationa nd orientation information to the end user each of the five traditional perceptionsa re the result of multiple sensory functionsw ithin the human body.Fort he purpose of thisr eview we classify the multitude of sensory systems into the Aristotle model of five key senses used to gather information about the outside world. Theh uman body represents an immense source of data collection aggregation and archiving relating to surroundings,b iochemical and temporal processes that allow the brain to understand the environment and its effecto n the body in real time.T he potential to access such ah uge reservoir of data that can be captured from existing bodily sensor systems is the next greatest challengei n sensor development. Rather than develop ever more complicated sensor devices the biggest challenge is how to interface with the existing bodily data streams and harvestt his information to aid in diagnostics,h ealth and wellbeing.Between detectiona nd conscious sensationt herei so ne more essential step that holds the key to accessing the human big data set:d igitalization. In computer terms this is what happens between the first tap of ak ey on ak eyboard and its visualization on the computers creen.W ith computers the processi sr elatively simple,p ushingakey simply closes ac ircuit generating ac urrentt hat travels to the processing unit, where its unique pattern is decoded and translated to the character [16].Inthe b...

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The how and why of identifying the hair cell mechano-electrical transduction channel

Cited by 17 publications

References 113 publications

The biophysics of piezo1 and piezo2 mechanosensitive channels

The biophysics of piezo1 and piezo2 mechanosensitive channels

Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells

Sensor Devices Inspired by the Five Senses: A Review

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