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

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 - Open Biol (2012)

Bottom Line: Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.

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.

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Related in: MedlinePlus

Hair cells in mouse cochlea express TRPC3 and TRPC6 and are normal in TRPC3/TRPC6 DKO mice. (a) Exemplar surface confocal sections of organ of Corti from WT and TRPC3/TRPC6 DKO mice (11 weeks old). Rhodamine-phalloidin (red) + nuclear DAPI (blue) staining of the cochlea showing outer hair cells and pillar cells of the basal turn (20× magnification). Inset shows 63× magnification. (b) In situ hybridization shows that TRPC3 and TRPC6 are found in the hair cells of P21 mice. Arrows indicate the location of inner hair cells (IHC). Sense probes for TRPC3 and TRPC6 produced little or no staining (see also electronic supplementary material, figure S3).
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RSOB120068F5: Hair cells in mouse cochlea express TRPC3 and TRPC6 and are normal in TRPC3/TRPC6 DKO mice. (a) Exemplar surface confocal sections of organ of Corti from WT and TRPC3/TRPC6 DKO mice (11 weeks old). Rhodamine-phalloidin (red) + nuclear DAPI (blue) staining of the cochlea showing outer hair cells and pillar cells of the basal turn (20× magnification). Inset shows 63× magnification. (b) In situ hybridization shows that TRPC3 and TRPC6 are found in the hair cells of P21 mice. Arrows indicate the location of inner hair cells (IHC). Sense probes for TRPC3 and TRPC6 produced little or no staining (see also electronic supplementary material, figure S3).

Mentions: We examined the sections of cochlea from adult WT and TRPC3/TRPC6 DKO mice that were age-matched. The cochleae from both WT and TRPC3/TRPC6 DKO mice appeared grossly morphologically normal when stained with rhodamine-phalloidin to highlight stereocilia. The density of outer and inner hair cells was similar in WT mice and in TRPC3/TRPC6 DKO mice in all regions of the cochlea, including those regions associated with responses to high-frequency stimuli (figure 5a).Figure 5.


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

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 - Open Biol (2012)

Hair cells in mouse cochlea express TRPC3 and TRPC6 and are normal in TRPC3/TRPC6 DKO mice. (a) Exemplar surface confocal sections of organ of Corti from WT and TRPC3/TRPC6 DKO mice (11 weeks old). Rhodamine-phalloidin (red) + nuclear DAPI (blue) staining of the cochlea showing outer hair cells and pillar cells of the basal turn (20× magnification). Inset shows 63× magnification. (b) In situ hybridization shows that TRPC3 and TRPC6 are found in the hair cells of P21 mice. Arrows indicate the location of inner hair cells (IHC). Sense probes for TRPC3 and TRPC6 produced little or no staining (see also electronic supplementary material, figure S3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376737&req=5

RSOB120068F5: Hair cells in mouse cochlea express TRPC3 and TRPC6 and are normal in TRPC3/TRPC6 DKO mice. (a) Exemplar surface confocal sections of organ of Corti from WT and TRPC3/TRPC6 DKO mice (11 weeks old). Rhodamine-phalloidin (red) + nuclear DAPI (blue) staining of the cochlea showing outer hair cells and pillar cells of the basal turn (20× magnification). Inset shows 63× magnification. (b) In situ hybridization shows that TRPC3 and TRPC6 are found in the hair cells of P21 mice. Arrows indicate the location of inner hair cells (IHC). Sense probes for TRPC3 and TRPC6 produced little or no staining (see also electronic supplementary material, figure S3).
Mentions: We examined the sections of cochlea from adult WT and TRPC3/TRPC6 DKO mice that were age-matched. The cochleae from both WT and TRPC3/TRPC6 DKO mice appeared grossly morphologically normal when stained with rhodamine-phalloidin to highlight stereocilia. The density of outer and inner hair cells was similar in WT mice and in TRPC3/TRPC6 DKO mice in all regions of the cochlea, including those regions associated with responses to high-frequency stimuli (figure 5a).Figure 5.

Bottom Line: Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.

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.

Show MeSH
Related in: MedlinePlus