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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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TRPC3 and TRPC6 are expressed in DRG neurons. In situ hybridization shows that TRPC3 (a) and TRPC6 (b) transcripts are found in almost all adult DRG neurons. The antisense TRPC3 probe does not stain neurons from TRPC3 knock-out mice and the antisense TRPC6 probe does not stain neurons from TRPC6 knock-out mice. See also electronic supplementary material, figure S1.
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RSOB120068F1: TRPC3 and TRPC6 are expressed in DRG neurons. In situ hybridization shows that TRPC3 (a) and TRPC6 (b) transcripts are found in almost all adult DRG neurons. The antisense TRPC3 probe does not stain neurons from TRPC3 knock-out mice and the antisense TRPC6 probe does not stain neurons from TRPC6 knock-out mice. See also electronic supplementary material, figure S1.

Mentions: Microarray studies of Nav1.8+ neurons and in situ hybridization studies of DRG neurons have shown that they express high levels of both TRPC3 and TRPC6 transcripts [22]. Immunohistochemical studies of TRP channels have been compromised by the lack of availability of specific antibodies. When we checked commercially available antisera to TRPC3 and TRPC6, they all stained knock-out tissue (not shown). We therefore used in situ hybridization with cRNA probes to TRPC3 and TRPC6, and found that both transcripts were present in all sensory neurons within DRG from 12-week-old mice, and the signals were lost in tissue from knock-out mice (figure 1). All postnatal DRG neurons were positive for TRPC3 transcripts in another study, but expression declined with age [23]. The in situ probes were transcript-specific, as shown by an analysis of expression in single knock-out mice.FigureĀ 1.


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)

TRPC3 and TRPC6 are expressed in DRG neurons. In situ hybridization shows that TRPC3 (a) and TRPC6 (b) transcripts are found in almost all adult DRG neurons. The antisense TRPC3 probe does not stain neurons from TRPC3 knock-out mice and the antisense TRPC6 probe does not stain neurons from TRPC6 knock-out mice. See also electronic supplementary material, figure S1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

RSOB120068F1: TRPC3 and TRPC6 are expressed in DRG neurons. In situ hybridization shows that TRPC3 (a) and TRPC6 (b) transcripts are found in almost all adult DRG neurons. The antisense TRPC3 probe does not stain neurons from TRPC3 knock-out mice and the antisense TRPC6 probe does not stain neurons from TRPC6 knock-out mice. See also electronic supplementary material, figure S1.
Mentions: Microarray studies of Nav1.8+ neurons and in situ hybridization studies of DRG neurons have shown that they express high levels of both TRPC3 and TRPC6 transcripts [22]. Immunohistochemical studies of TRP channels have been compromised by the lack of availability of specific antibodies. When we checked commercially available antisera to TRPC3 and TRPC6, they all stained knock-out tissue (not shown). We therefore used in situ hybridization with cRNA probes to TRPC3 and TRPC6, and found that both transcripts were present in all sensory neurons within DRG from 12-week-old mice, and the signals were lost in tissue from knock-out mice (figure 1). All postnatal DRG neurons were positive for TRPC3 transcripts in another study, but expression declined with age [23]. The in situ probes were transcript-specific, as shown by an analysis of expression in single knock-out mice.FigureĀ 1.

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