**5.2 Mechanosensitive channels and Ca2+ signaling**

Mechanosensitive ionic channels are transmembrane proteins that form a pore structure across the cell membrane. These channels are linked to the cytoskeletal proteins; thus, changes in cytoskeletal stresses may open the mechanosensitive channels [94, 95]. Similarly, changes in membrane tension could also alter the channel configuration.

Several MSCs have been identified in astrocytes that are members of the transient receptor potential (TRP) family including TRPV4, TRPC1, TRPC5, and TRPA1 [96–98, 99]. Studies of sensory neurons have suggested that Piezo channels play an important role in brain cells [100, 101]. Piezo-type MSCs are also present in astrocytes that can be inhibited with specific Piezo channel inhibitor [102]. Using an astrocyte model, a recent study has shown that N-Methyl-D-aspartic acid receptors (NMDARs) are the primary Ca2+ source in astrocytes and fluid shear stimuli can activate NMDARs in the absence of agonists [57].

The fluid shear forces can alter the channel activities via several mechanisms. They can modify the cytoskeletal stresses, and the cytoskeleton under high tension can pull the channel proteins via their links. Many MSCs are known to link with the actin cytoskeleton with cross-linking proteins [103–105]. In astrocytes and neurons, α-actinin binds to NMDA receptors, providing a mechanical link between NMDA receptors with the underlying cytoskeleton [106]. Shear stress can also cause transient deformation and bending of the lipid bilayer, altering the MSCs directly [107–109]. Most likely, both mechanisms are correlated.
