Sensory mechanotransduction at membrane-matrix interfaces.

Kate Poole,Gary R Lewin,Mirko Moroni

doi:10.1007/s00424-014-1563-6

Abstract

Sensory cells specialized to detect extremely small mechanical changes are common to the auditory and somatosensory systems. It is widely accepted that mechanosensitive channels form the core of the mechanoelectrical transduction in hair cells as well as the somatic sensory neurons that underlie the sense of touch and mechanical pain. Here, we will review how the activation of such channels can be measured in a meaningful physiological context. In particular, we will discuss the idea that mechanosensitive channels normally occur in transmembrane complexes that are anchored to extracellular matrix components (ECM) both in vitro and in vivo. One component of such complexes in sensory neurons is the integral membrane scaffold protein STOML3 which is a robust physiological regulator of native mechanosensitive currents. In order to better characterize such channels in transmembrane complexes, we developed a new electrophysiological method that enables the quantification of mechanosensitive current amplitude and kinetics when activated by a defined matrix movement in cultured cells. The results of such studies strongly support the idea that ion channels in transmembrane complexes are highly tuned to detect movement of the cell membrane in relation to the ECM.

Highlights

The ability of cells to rapidly transform mechanical deflection or changes in applied force into an electrical signal is aK
Functional mechanoelectrical transduction (MET) channels are placed at the tips of the hair cell stereocilia and require an intact tip-link connector between stereocilia in order to gate in response to bundle displacements of a few tens of nanometers [3, 34]
The presence of cadherin-23 or protocadherin-15 or intact tip links appear to be absolute requirements for hair cell mechanotransduction [3, 99]. In another well-studied example of a mechanoreceptor, the body touch neurons of the nematode Caenorhabditis elegans and the genetic and electrophysiological studies have definitively demonstrated that the Deg/ ENaC family members MEC-4 and MEC-10 form the core of Pflugers Arch - Eur J Physiol (2015) 467:121–132 a mechanosensitive complex in these neurons [2, 33, 82, 83]

Summary

Introduction

The ability of cells to rapidly transform mechanical deflection or changes in applied force into an electrical signal is aK. Matrix interactions relevant for fast mechanotransduction in sensory neurons In contrast to studies on the sensory hair cell, it has so far proved impossible to make direct high-resolution intracellular recordings from mammalian afferent endings near the site of mechanosensory transduction. Several groups used direct mechanical stimulation of the cell body or neurites of a cultured rodent’s dorsal root ganglion neurons to show that rapidly activating mechanically gated currents can be readily measured in these cells [18, 31, 48, 75].

Results

Conclusion