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

The mechanosensor Transient Receptor Potential Vanilloid Member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation. Am J Physiol Gastrointest Liver Physiol. 2019 Nov 25;: Authors: Li Q, Kresge C, Boggs K, Scott J, Feranchak A Abstract 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 cholangioc...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research