The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals

Abstract

Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a) the development of mechanoresponsive structures, ( b) acute mechanical sensing, and ( c) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc

“…TRPV4 is a critical osmotic and mechanical regulator in multiple organ systems and cell types, 24–26 and we demonstrate here that it robustly responds to mechanical loading in the intact IVD. There are also a number of known mechanoreceptors, including the TRP family and PIEZO ion channels that regulate Ca 2+ flux, that could participate in IVD's adaptation to sustained loading 61,62 .…”

Modulation of TRPV4 Protects against Degeneration Induced by Sustained Loading and Promotes Matrix Synthesis in the Intervertebral Disc

“…TRPV4 is a critical osmotic and mechanical regulator in multiple organs systems and cell types, 24–26 and we demonstrate here that it robustly responds to mechanical loading in the intact IVD. There are also a number of known mechanoreceptors, including the TRP family and PIEZO ion channels that regulate of Ca 2+ flux, that could participate in IVD’s adaptation to sustained loading.…”

“…22,23 TRPV4 is an important osmo-and mechano-regulator in a variety of cell types, including chondrocytes, osteocytes, cardiovascular endothelial cells, and renal epithelial cells. 24–26 TRPV4 is crucial for mechanosensing in articular cartilage and has been shown to regulate the anabolic response of chondrocytes to mechanical loading. 27–29 Similar to articular cartilage in both its motion-enabling joint function and matrix constituents, the mechanosensing mechanisms may be conserved in the IVD.…”

Molecular Markers of Mechanosensation in Glycinergic Neurons in the Avian Lumbosacral Spinal Cord

“…The transmembrane channel-like proteins 1 and 2 (TMC 1/2) have been identified as the mechanosensitive components of the mechanoelectrical transduction apparatus in hair cells ( Kurima et al, 2015 ; Jia et al, 2020 ). Piezo1 and piezo2 are mechanically-activated components of transmembrane channels ( Coste et al, 2010 , 2012 ) involved in homeostatic and somatosensory functions, respectively (for review, see Poole, 2021 ; Szczot et al, 2021 ). Pkd2l1, the marker of CSF-cNs mentioned above, is part of the polycystic family of transient receptor potential (TRP) channels, many of which are implicated in mechanotransduction (for review, see Christensen and Corey, 2007 ; Delmas et al, 2011 ).…”