Defining features of the hair cell mechanoelectrical transducer channel

Fettiplace, Robert

doi:10.1007/s00424-009-0683-x

Cited by 55 publications

(62 citation statements)

References 73 publications

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“…Similarly, interaction of QX-314 with permeating monovalent ions can explain the sidedness with which it acts, with inward current flow by monovalents effectively displacing internally applied QX-314 from its binding site, so that it blocks only outward current, and similarly for outward current flow displacing externally applied QX-314. The ability of QX-314 and large quaternary ammonium molecules to act as permeant blockers in TRPV1 is reminiscent of the behavior of large permeant blockers like the cationic antibiotic dihydrostreptomycin in the hair cell mechanoelectrical transducer (MET) channel, another large-pore channel (Farris et al 2004;Fettiplace 2009). …”

Section: Discussionmentioning

confidence: 99%

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

Puopolo

Binshtok

Yao

et al. 2013

Journal of Neurophysiology

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Puopolo M, Binshtok AM, Yao GL, Oh SB, Woolf CJ, Bean BP. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. J Neurophysiol 109: 1704 -1712, 2013. First published January 9, 2013 doi:10.1152 doi:10. /jn.00012.2013) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of "pore dilation" previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with P QX-314 /P Cs ϭ 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50 -100 M. We conclude that QX-314 is directly permeant in the "standard" pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry.

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Section: Discussionmentioning

confidence: 99%

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

Puopolo

Binshtok

Yao

et al. 2013

Journal of Neurophysiology

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“…Furthermore, the screen revealed TRPP3 and PKD1L3 RNA expression patterns that were correlated with the acquisition of sensory transduction in outer hair cells (Lelli et al, J Neurophysiol. 101:2961-2973, 2009). Numerous spatiotemporal expression gradients were identified many of which may contribute to the normal functional development of the mouse cochlea.…”

Section: Introductionmentioning

confidence: 99%

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

Asai

Holt

Géléoc

2009

JARO

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TRP genes encode a diverse family of ion channels which have been implicated in many sensory functions. Because several TRP channels have similar properties to the elusive hair cell transduction channel, recent attention has focused on TRP gene expression in the inner ear. At least four TRP genes are known to be expressed in hair cells: TRPC3, TRPV4, TRPA1, and TRPML3. However, there is little evidence supporting any of these as a component of the transduction complex. Other less well-characterized TRP channels are expressed in the inner ear, in particular, within the organ of Corti. Because of their potential role in sensory function, we investigated the developmental expression of RNA that encodes all 33 TRP subunits as well as several splice variants. We designed a quantitative PCR screen using cochlear samples acquired before, during, and after the time when mechanotransduction is acquired in sensory hair cells (embryonic day 17 to postnatal day 8). Cochleas, which included the organ of Corti, stria vascularis, and Reissner's membrane, were subdivided into four equal quadrants which allowed for regional comparison during development. Expression of RNA transcripts that encoded 33 TRP subunits plus several splice forms and beta-actin were quantified in 28 samples for a total of 1,092 individual measurements, each done in triplicate. We detected RNA that encoded all TRP channels except two: TRPC7 and TRPM8. The largest changes in RNA expression were for TRPA1 (9100-fold), which suggested that these subunits may contribute to normal cochlear function. Furthermore, the screen revealed TRPP3 and PKD1L3 RNA expression patterns that were correlated with the acquisition of sensory transduction in outer hair cells (Lelli et al., J Neurophysiol. 101:2961-2973, 2009). Numerous spatiotemporal expression gradients were identified many of which may contribute to the normal functional development of the mouse cochlea.

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“…Sound-induced deflection of a hair bundle in the direction of the longest stereocilia stretches the tip link, thus opening the MET channel and initiating mechanotransduction (18,19,51). In the vertebrate inner ear, hair bundles are bathed in endolymph in which resides high K ϩ , and mechanotransduction is predominantly activated by K ϩ entry through MET channels (18,65). However, electrophysiological analysis of isolated hair cells showed that MET channel is a nonselective cation channel with high Ca 2ϩ permeability, which passes Ca 2ϩ at least fives times better than it does Na ϩ and K ϩ (18).…”

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confidence: 99%

“…In the prevailing model, AGs in the endolymph are taken up by hair cells through the mechanotransducer (MET) channel (1, 36, 61). Entry of AGs into hair cells is thought to trigger formation of reactive oxygen species and activation of caspase signaling and ultimately lead to cell apoptosis (62).MET channels are located at the tips of actin-filled stereocilia (hair bundles) of hair cells and are gated by an elastic element, the "tip link," connecting stereocilia and kinocilia (18,19,44,51). Sound-induced deflection of a hair bundle in the direction of the longest stereocilia stretches the tip link, thus opening the MET channel and initiating mechanotransduction (18,19,51).…”

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confidence: 99%

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Extracellular Ca²⁺ and Mg²⁺ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca²⁺ entry in zebrafish hair cells: an in vivo study with the SIET

Chuang

Hung

et al. 2013

American Journal of Physiology-Cell Physiology

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Zebrafish lateral-line hair cells are an in vivo model for studying hair cell development, function, and ototoxicity. However, the molecular identification and properties of the mechanotransducer (MET) channel in hair cells are still controversial. In this study, a noninvasive electrophysiological method, the scanning ion-electrode technique (SIET), was applied for the first time to investigate properties of MET channels in intact zebrafish embryos. With the use of a Ca(2+)-selective microelectrode to deflect hair bundles and simultaneously record the Ca(2+) flux, the inward Ca(2+) flux was detected at stereocilia of hair cells in 2- to ~4-day postfertilization embryos. Ca(2+) influx was blocked by MET channel blockers (BAPTA, La(3+), Gd(3+), and curare). In addition, 10 μM aminoglycoside antibiotics (neomycin and gentamicin) were found to effectively block Ca(2+) influx within 10 min. Elevating the external Ca(2+) level (0.2-2 mM) neutralized the effects of neomycin and gentamicin. However, elevating the Mg(2+) level up to 5 mM neutralized blockade by gentamicin but not by neomycin. This study demonstrated MET channel-mediated Ca(2+) entry at hair cells and showed that the SIET to be a sensitive approach for functionally assaying MET channels in zebrafish.

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Defining features of the hair cell mechanoelectrical transducer channel

Cited by 55 publications

References 73 publications

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

Extracellular Ca²⁺ and Mg²⁺ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca²⁺ entry in zebrafish hair cells: an in vivo study with the SIET

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Defining features of the hair cell mechanoelectrical transducer channel

Cited by 55 publications

References 73 publications

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

Extracellular Ca2+ and Mg2+ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca2+ entry in zebrafish hair cells: an in vivo study with the SIET

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Extracellular Ca²⁺ and Mg²⁺ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca²⁺ entry in zebrafish hair cells: an in vivo study with the SIET