TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells

Kathryn Quick; Jing Zhao; Niels Eijkelkamp; John E. Linley; Francois Rugiero; James J. Cox; Ramin Raouf; Martine Gringhuis; Jane E. Sexton; Joel Abramowitz; Ruth Taylor; Andy Forge; Jonathan Ashmore; Nerissa Kirkwood; Corne J. Kros; Guy P. Richardson; Marc Freichel; Veit Flockerzi; Lutz Birnbaumer; John N. Wood

doi:10.1098/rsob.120068

TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells

Kathryn Quick, Jing Zhao, Niels Eijkelkamp, John E. Linley, Francois Rugiero, James J. Cox, Ramin Raouf, Martine Gringhuis, Jane E. Sexton, Joel Abramowitz, Ruth Taylor, Andy Forge, Jonathan Ashmore, Nerissa Kirkwood, Corne J. Kros, Guy P. Richardson, Marc Freichel, Veit Flockerzi, Lutz Birnbaumer, John N. Wood^*

^*Corresponding author for this work

Wolfson SPaRC

Research output: Contribution to journal › Article › peer-review

137 Citations (Scopus)

Abstract

Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes.

Original language	English
Article number	120068
Number of pages	14
Journal	Open Biology
Volume	2
Issue number	5
DOIs	https://doi.org/10.1098/rsob.120068
Publication status	Published - May 2012

Keywords

MOLECULAR-BASIS
MICE
GUINEA-PIG
PERMEANT BLOCKER
hearing
MOUSE INNER-EAR
touch
MECHANOSENSITIVE ION CHANNELS
MECHANOELECTRICAL TRANSDUCTION
EXPRESSION
CURRENTS
mechanosensation
HEARING IMPAIRMENT

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1098/rsob.120068

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Quick, K., Zhao, J., Eijkelkamp, N., Linley, J. E., Rugiero, F., Cox, J. J., Raouf, R., Gringhuis, M., Sexton, J. E., Abramowitz, J., Taylor, R., Forge, A., Ashmore, J., Kirkwood, N., Kros, C. J., Richardson, G. P., Freichel, M., Flockerzi, V., Birnbaumer, L., & Wood, J. N. (2012). TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells. Open Biology, 2(5), Article 120068. https://doi.org/10.1098/rsob.120068

@article{494131d346b044608a5aa6d1ef92aeb4,

title = "TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells",

abstract = "Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes.",

keywords = "MOLECULAR-BASIS, MICE, GUINEA-PIG, PERMEANT BLOCKER, hearing, MOUSE INNER-EAR, touch, MECHANOSENSITIVE ION CHANNELS, MECHANOELECTRICAL TRANSDUCTION, EXPRESSION, CURRENTS, mechanosensation, HEARING IMPAIRMENT",

author = "Kathryn Quick and Jing Zhao and Niels Eijkelkamp and Linley, {John E.} and Francois Rugiero and Cox, {James J.} and Ramin Raouf and Martine Gringhuis and Sexton, {Jane E.} and Joel Abramowitz and Ruth Taylor and Andy Forge and Jonathan Ashmore and Nerissa Kirkwood and Kros, {Corne J.} and Richardson, {Guy P.} and Marc Freichel and Veit Flockerzi and Lutz Birnbaumer and Wood, {John N.}",

year = "2012",

month = may,

doi = "10.1098/rsob.120068",

language = "English",

volume = "2",

journal = "Open Biology",

issn = "2046-2441",

publisher = "Royal Society Publishing",

number = "5",

}

Quick, K, Zhao, J, Eijkelkamp, N, Linley, JE, Rugiero, F, Cox, JJ, Raouf, R, Gringhuis, M, Sexton, JE, Abramowitz, J, Taylor, R, Forge, A, Ashmore, J, Kirkwood, N, Kros, CJ, Richardson, GP, Freichel, M, Flockerzi, V, Birnbaumer, L & Wood, JN 2012, 'TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells', Open Biology, vol. 2, no. 5, 120068. https://doi.org/10.1098/rsob.120068

TY - JOUR

T1 - TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells

AU - Quick, Kathryn

AU - Zhao, Jing

AU - Eijkelkamp, Niels

AU - Linley, John E.

AU - Rugiero, Francois

AU - Cox, James J.

AU - Raouf, Ramin

AU - Gringhuis, Martine

AU - Sexton, Jane E.

AU - Abramowitz, Joel

AU - Taylor, Ruth

AU - Forge, Andy

AU - Ashmore, Jonathan

AU - Kirkwood, Nerissa

AU - Kros, Corne J.

AU - Richardson, Guy P.

AU - Freichel, Marc

AU - Flockerzi, Veit

AU - Birnbaumer, Lutz

AU - Wood, John N.

PY - 2012/5

Y1 - 2012/5

N2 - Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes.

AB - Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes.

KW - MOLECULAR-BASIS

KW - MICE

KW - GUINEA-PIG

KW - PERMEANT BLOCKER

KW - hearing

KW - MOUSE INNER-EAR

KW - touch

KW - MECHANOSENSITIVE ION CHANNELS

KW - MECHANOELECTRICAL TRANSDUCTION

KW - EXPRESSION

KW - CURRENTS

KW - mechanosensation

KW - HEARING IMPAIRMENT

U2 - 10.1098/rsob.120068

DO - 10.1098/rsob.120068

M3 - Article

SN - 2046-2441

VL - 2

JO - Open Biology

JF - Open Biology

IS - 5

M1 - 120068

ER -

TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells

Abstract

Keywords

UN SDGs

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