Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice

PLoS One. 2016 May 19;11(5):e0155577. doi: 10.1371/journal.pone.0155577. eCollection 2016.

Abstract

Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Cochlea / physiology
  • Ear, Inner / physiology
  • Evoked Potentials, Auditory, Brain Stem / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hair Cells, Auditory / physiology*
  • Hearing*
  • Mechanotransduction, Cellular
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Patch-Clamp Techniques
  • Receptors, Cell Surface / genetics
  • TRPM Cation Channels / genetics*
  • TRPP Cation Channels / genetics
  • Transient Receptor Potential Channels / genetics*

Substances

  • Calcium Channels
  • Membrane Glycoproteins
  • PKD1L3 protein, mouse
  • Pkd2l1 protein, mouse
  • Pkd2l2 protein, mouse
  • Receptors, Cell Surface
  • TRPM Cation Channels
  • TRPM2 protein, mouse
  • TRPP Cation Channels
  • Transient Receptor Potential Channels
  • polycystic kidney disease 2 protein