Add like
Add dislike
Add to saved papers

The mechanosensor Transient Receptor Potential Vanilloid Member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation.

Mechanosensitive signaling has emerged as a mechanism for the regulation of cholangiocyte transport and bile formation. The mechanical effect of fluid-flow, or shear, at the apical membrane of cholangiocytes regulates secretion through a process involving increases in [Ca2+]i and activation of Ca2+-activated Cl- channels. However, the initiating steps translating shear force to increases in [Ca2+]i are unknown. Transient Receptor Potential Vanilloid Member 4 (TRPV4), a non-selective cation channel present in the apical membrane of cholangiocytes, has been proposed as a potential mechanosensor. The aim of the current studies was to determine the potential role of TRPV4 in initiating mechanosensitive signaling in response to fluid-flow in cholangiocytes. TRPV4 expression was confirmed in both small and large mouse cholangiocytes. Exposure of cells to either fluid-flow or specific TRPV4 pharmacologic agonists rapidly increased both [Ca2+]i and membrane cation currents. Both flow- and agonist-stimulated currents displayed identical biophysical properties and were inhibited in the presence of TRPV4 antagonists or in cells after transfection with TRPV4 siRNA. Transfection of mouse cholangiocytes with a TRPV4-EGFP construct increased the expression of TRPV4 and the magnitude of flow-stimulated currents. Lastly, intravenous administration of a specific TRPV4 agonist significantly increased bile flow in mice. The findings are consistent with a model in which activation of cholangiocyte TRPV4 translates shear force to an acute rise in membrane cation permeability, [Ca2+]i, and bile flow. Understanding the role of mechanosensitive transport pathways may provide novel insights to modulate bile flow for the treatment of cholestatic liver disorders.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app