Exp Neurobiol.  2017 Apr;26(2):71-81. 10.5607/en.2017.26.2.71.

Flow Shear Stress Enhances the Proliferative Potential of Cultured Radial Glial Cells Possibly Via an Activation of Mechanosensitive Calcium Channel

Affiliations
  • 1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea. cjl@kist.re.kr
  • 2Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
  • 3Center for Glia-Neuron Interaction, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
  • 4School of Biomedical Engineering, College of Health Science, Korea University, Seoul 02841, Korea.
  • 5Department of Bio-convergence Engineering, College of Health Science, Korea University, Seoul 02841, Korea.

Abstract

Radial glial cells (RGCs) which function as neural stem cells are known to be non-excitable and their proliferation depends on the intracellular calcium (Ca²âº) level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)-mediated Ca²âº release and Ca²âº entry through various Ca²âº 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 Ca²âº 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 Ca²âº 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 Ca²âº level, which disappeared under the extracellular Ca²âº-free condition. Our results suggest that the shear stress by CSF flow possibly activates mechanosensitive Ca²âº channels, which gives rise to a Ca²âº entry which enhances the proliferative capacity of RGCs.

Keyword

Radial glial cell; Shear stress; Mechanosensitive ion channel

MeSH Terms

Brain
Calcium Channels*
Calcium*
Cerebrospinal Fluid
Ependymoglial Cells*
Inositol 1,4,5-Trisphosphate
Ion Channels
Lab-On-A-Chip Devices
Microfluidics
Neural Stem Cells
Calcium
Calcium Channels
Inositol 1,4,5-Trisphosphate
Ion Channels
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