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KMID : 0892920170260020071
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Experimental Neurobiology
2017 Volume.26 No. 2 p.71 ~ p.81
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Flow Shear Stress Enhances the Proliferative Potential of Cultured Radial Glial Cells Possibly Via an Activation of Mechanosensitive Calcium Channel
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Park Min-Gu
Jang Hee-Yeong
Lee Sang-Hoon
Lee C. Justin
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Abstract
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Radial glial cells (RGCs) which function as neural stem cells are known to be non-excitable and their proliferation depends on the intracellular calcium (Ca2+) level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release and Ca2+ entry through various Ca2+ channels are involved in the proliferation of RGCs. Furthermore, RGCs line the ventricular wall and are exposed to a shear stress due to a physical contact with the cerebrospinal fluid (CSF). However, little is known about how the Ca2+ entry through mechanosensitive ion channels affects the proliferation of RGCs. Hence, we hypothesized that shear stress due to a flow of CSF boosts the proliferative potential of RGCs possibly via an activation of mechanosensitive Ca2+ channel during the embryonic brain development. Here, we developed a new microfluidic two-dimensional culture system to establish a link between the flow shear stress and the proliferative activity of cultured RGCs. Using this microfluidic device, we successfully visualized the artificial CSF and RGCs in direct contact and found a significant enhancement of proliferative capacity of RGCs in response to increased shear stress. To determine if there are any mechanosensitive ion channels involved, a mechanical stimulation by poking was given to individual RGCs. We found that a poking on radial glial cell induced an increase in intracellular Ca2+ level, which disappeared under the extracellular Ca2+-free condition. Our results suggest that the shear stress by CSF flow possibly activates mechanosensitive Ca2+ channels, which gives rise to a Ca2+ entry which enhances the proliferative capacity of RGCs.
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KEYWORD
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Radial glial cell, Shear stress, Mechanosensitive ion channel
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