Mechanically Gated Ion Channels in Mammalian Hair Cells

Abstract

Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET) channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS)/LHFPL5, transmembrane inner ear (TMIE) and transmembrane channel-like proteins 1 and 2 (TMC1/2). However, there remains considerable uncertainty regarding the molecules that form the channel pore. In addition to the sensory MET channel, hair cells express the mechanically gated ion channel PIEZO2, which is localized near the base of stereocilia and not essential for sensory transduction. The function of PIEZO2 in hair cells is not entirely clear but it might have a role in damage sensing and repair processes. Additional stretch-activated channels of unknown molecular identity and function have been found to localize at the basolateral membrane of hair cells. Here, we review current knowledge regarding the different mechanically gated ion channels in hair cells and discuss open questions concerning their molecular composition and function.

Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

“…Accordingly the MET current is lost when the tip link is disrupted by chelating calcium with BAPTA. The tip link is made of a homodimer of cadherin 23 (CDH23) at the upper end anchored to the stereocilium through the Usher complex Myo7a along with other myosins, and protocadherin related 15 (PCDH15) at the lower end interacting with the MET channel (Fettiplace, 2016;Ge et al, 2018;Maeda et al, 2014;Qiu and Muller, 2018;Richardson et al, 2011)( Figure 5D). The MET channel opens in the microseconds range following positive deflection of the hair cell bundle, indicating that channel mechanical activation is direct (i.e.…”

Physiological Basis of Noise-Induced Hearing Loss in a Tympanal Ear

“…Explanation 2: a decrease in the transduction channel number The second explanation is particularly hard to unequivocally test because the protein/s that form/s the transduction channel have, controversially, not been identified in insects -or indeed any animal ear (although in mammals, it seems, they are getting close (Qiu & Müller, 2018)). We showed no change in expression of the three genes that compose the two putative candidate mechanotransduction ion channels.…”

A screen for gene paralogies delineating evolutionary branching order of early Metazoa

“…We thus propose that the evolutionary diversification of the Tmc channels throughout Metazoa, including the independent diversification within Ctenophora (Fig. 5 Simply speaking, no single molecule has been identified to be associated with all mechanotransduction across phyla such as the ecdysozoan TRP channels also found in bony fish but absent in mammals (BEISEL et al 2010;COX et al 2018b;QIU AND MULLER 2018 (FRITZSCH et al 2006;FRITZSCH et al 2015). Recent work also establishes that ecdysozoan Tmc123 paralogs function in body kinesthesia (proprioception), sensory control of locomotion or egg-laying behavior via membrane depolarization, and nociception (GUO et al 2016;WANG et al 2016;YUE et al 2018).…”

“…We find that a phylogenetic analysis of gene duplications of the transmembrane channels (TMCs), a large family of ion leak channels with roles in mechanotransduction (DELMAS AND COSTE 2013; PAN et al 2013;BALLESTEROS et al 2018;PAN et al 2018;QIU AND MULLER 2018;JIA et al 2019), excludes ctenophores from a eumetazoan super-clade composed of Bilateria, Cnidaria, and Placozoa (Fig. 5).…”