Mechanosensitive Cl− secretion in biliary epithelium mediated through TMEM16A
| Autor: | Amal K. Dutta, Kangmee Woo, Andrew P. Feranchak, Al Karim Khimji, Charles Kresge |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Protein Kinase C-alpha Physiology Cystic Fibrosis Transmembrane Conductance Regulator Biology digestive system Cholangiocyte Epithelium Cell Line Cell membrane Mice Adenosine Triphosphate Chlorides Chloride Channels Physiology (medical) Internal medicine medicine Animals Humans Calcium Signaling Gene Silencing Biliary Tract Anoctamin-1 Hepatology Bile duct Receptors Purinergic P2 Viscosity Cell Membrane Gastroenterology Cystic fibrosis transmembrane conductance regulator Cell biology Neoplasm Proteins Perfusion Liver and Biliary Tract medicine.anatomical_structure Endocrinology Biliary tract Hepatocyte biology.protein Mechanosensitive channels |
| Popis: | Bile formation by the liver is initiated by canalicular transport at the hepatocyte membrane, leading to an increase in ductular bile flow. Thus, bile duct epithelial cells (cholangiocytes), which contribute to the volume and dilution of bile through regulated Cl− transport, are exposed to changes in flow and shear force at the apical membrane. The aim of the present study was to determine if fluid flow, or shear stress, is a signal regulating cholangiocyte transport. The results demonstrate that, in human and mouse biliary cells, fluid flow, or shear, increases Cl− currents and identify TMEM16A, a Ca2+-activated Cl− channel, as the operative channel. Furthermore, activation of TMEM16A by flow is dependent on PKCα through a process involving extracellular ATP, binding purinergic P2 receptors, and increases in intracellular Ca2+ concentration. These studies represent the initial characterization of mechanosensitive Cl− currents mediated by TMEM16A. Identification of this novel mechanosensitive secretory pathway provides new insight into bile formation and suggests new therapeutic targets to enhance bile formation in the treatment of cholestatic liver disorders. |
| Databáze: | OpenAIRE |
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