Abstract
Transient receptor potential channels have diverse roles in mechanosensation. Evidence is accumulating that members of the canonical subfamily of TRP channels (TRPC) are involved in touch and hearing. Characteristic features of TRP channels include their high structural homology and their propensity to form heteromeric complexes which suggests potential functional redundancy. We previously showed that TRPC3 and TRPC6 double knockout animals have deficits in light touch and hearing whilst single knockouts were apparently normal. We have extended these studies to analyse deficits in global quadruple TRPC1, 3, 5 and 6 null mutant mice. We examined both touch and hearing in behavioural and electrophysiological assays, and provide evidence that the quadruple knockout mice have larger deficits than the TRPC3 TRPC6 double knockouts. Mechano-electrical transducer currents of cochlear outer hair cells were however normal. This suggests that TRPC1, TRPC3, TRPC5 and TRPC6 channels contribute to cutaneous and auditory mechanosensation in a combinatorial manner, but have no direct role in cochlear mechanotransduction.
Highlights
The mechanisms underlying mechanotransduction in mammals are incompletely understood
Transient receptor potential (TRP) channels (TRPC) channels are ubiquitously expressed in the inner ear in structures including the organ of Corti and the spiral and vestibular ganglia [29] suggesting that, in addition to TRPC3 and TRPC6, there is potential for other TRPC subunits to play a mechanosensory role in hearing
TRPC1, TRPC3, TRPC5 and TRPC6 are all expressed in sensory ganglia [10,31] and TRPC3 and TRPC6 have been shown to be expressed in cochlear hair cells [23]
Summary
The mechanisms underlying mechanotransduction in mammals are incompletely understood. A single cell RNA sequencing study determined a non-peptidergic subset of neurons which express all four TRPC subunits [30] meaning there is substantial potential for interaction between different combinations of these TRPC subunits. TRPC1 and TRPC6 are coexpressed with TRPV4 in dorsal root ganglia (DRG) and it has been proposed that they may act in concert to mediate mechanical hypersensitivity in neuropathic and inflammatory pain states [1]. TRPC1 and TRPC5 confer sensitivity to osmotically induced membrane stretch in cultured DRG neurons and HEK293 cells, respectively [13,28]. TRPC channels are ubiquitously expressed in the inner ear in structures including the organ of Corti and the spiral and vestibular ganglia [29] suggesting that, in addition to TRPC3 and TRPC6, there is potential for other TRPC subunits to play a mechanosensory role in hearing
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