Mechanosensitive channels
[5] They are the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst).
[6] MSCs function as mechanotransducers capable of generating both electrical and ion flux signals as a response to external or internal[7] stimuli.
[9] Mechanosensitive channels were discovered in 1983 in the skeletal muscle of embryonic chicks[10] by Falguni Guharay and Frederick Sachs.
[50][51] Stretch-activated ion channels are required for the initial formation of an action potential from a mechanical stimulus, for example by the mechanoreceptors in vibrissae (whiskers) of some animals such as rodents.
Stretch-activated ion channels are located on these mechanoreceptor cells and serve to lower the action potential threshold, thus making the afferent nerves more sensitive to stimulation.
[53][54] They are expressed in sensory modalities including taste, hearing, smell, heat sensation, volume control, and vision.
[61] The TRP superfamily of channels are found in sensory receptor cells that are involved in heat sensation, taste, smell, touch, and osmotic and volume regulation.
Sound waves are able to bend the stereocilia and open up ion channels leading to the creation of nerve impulses.
Proteins of the extracellular matrix and cytoskeleton are tethered to extra - and intra-cytoplasmic domains, respectively, of the stretch-activated ion channels.
[53] All known stretch-activated ion channels in prokaryotic cells have been found to be opened by direct deformation of the lipid bilayer membrane.
[55] Mechanical deformation of the cell membrane can be achieved by a number of experimental interventions, including magnetic actuation of nanoparticles.
These channels function in tandem-mode and are responsible of turgor regulation in bacteria; when activated by changes in the osmotic pressure.
Mutagenesis studies showed that when both genes YggB and KefA were deleted MscS lost its function, but maintain MscL and MscM, but mutants deficient of YggB and MscL showed that the function of those channel is to open in respond to pressure range right before cell rupture.
The TM3 is highly conserved in MscS family and it is thought to play an important role in MS prokaryotic gating.
[75] MscS is a small protein composed of 286 amino acid residues activated by both tension in the lipid bilayer and voltage; in 2002 Vasquez et al.[76] detailed this process and showed that during the change from closed state to open state the TM1 tilt and rotate making TM2 being exposed to the membrane and the TM3 helices expand, tilt, and rotate.
[79] In 1998 the homolog MscL from mycobacterium tuberculosis Tb-MscL was elucidated at closed state by X ray crystallography at 3.5 Å resolution.
When tension is applied to the membrane the transmembrane barrel-like structure expand and stretch apart the region S1-TM1 allowing the channel to open.
In the case of the prokaryotic protein channels MscS and MscL both are gated by tension in the lipid bilayer, thus suggesting an important role in such a complex structures.
The tension in the membrane bilayer has been extensively studied, simple intrinsic properties of the lipids can account for the contributions in the free energy of the open, intermediate, and close state of the MS channels.
[88] Piezo2 is expressed in sensory neurons of the dorsal root and trigeminal ganglia indicating that it may play a role in touch sensation.
Recent studies have revealed a new role of mechanosensitive pathways in which naive mesenchymal stem cells are committed to a particular lineage based on the elasticity of its surrounding matrix.
[55][56] Stretch-activated ion channels have been shown to detect vibration, pressure, stretch, touch, sounds, tastes, smell, heat, volume, and vision.
[56] Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were published in 1984.
The depolarization at five minutes was the cytoskeleton snapping which subsequently caused the channel to sense the mechanical deformations and thereby respond to the stimuli.
These ASIC subunits likely form tetramers with varying kinetics, pH sensitivity, tissue distribution, and pharmacological properties.
[53] There are seven subfamilies within the TRP superfamily: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin), and TRPN (NOMPC-like).
[53] TRP channels are typically non-selective, although a few are selective for calcium or hydrated magnesium ions, and are composed of integral membrane proteins.
[56] Some examples are TRPV4, which mediates mechanical load in a variety of tissues, including the liver, heart, lung, trachea, testis, spleen, salivary glands, cochlea, and vascular endothelial cells,[56] as well as TRPC1 and TRPC6, which are involved in muscle mechanosensation.
[95] Other examples include TREK-1 and TRAAK which are found in mammalian neurons and are classified as potassium channels in the tandem pore domain class[96][97] and "MID-1" (also known as "MCLC" or CLCC1.
)[98][99] The six K2P channel subfamilies are regulated by various physical, cellular, and pharmacological stimulants, including membrane stretch, heat, pH change, calcium flux, and protein kinases.
