TY - JOUR
T1 - Regulated ion transport in mouse liver cyst epithelial cells
AU - Doctor, R. Brian
AU - Johnson, Sylene
AU - Brodsky, Kelley S.
AU - Amura, Claudia R.
AU - Gattone, Vincent
AU - Fitz, J. Gregory
N1 - Funding Information:
The authors would like to acknowledge the technical efforts and expertise of Rolf Dahl in the microscopy studies. The pkd2 mouse model was graciously provided by Dr. Stephan Somlo (Yale University). This work was supported by an NIH grant to R.B.D. (P01 DK-34039), NIH grants to J.G.F. (DK-43278 and DK-46082) and a PKD Foundation grant to R.B.D. (PKDF 109a2r).
PY - 2007/3
Y1 - 2007/3
N2 - Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl- secretion and Na+ absorption. Na+ absorption was amiloride-sensitive, suggesting the activation of epithelial sodium channels (ENaC). Further, both cAMPi and extracellular ATP induced robust secretory responses. Western blotting and immunohistologic analysis of liver cyst epithelia demonstrated expression of P2X4, a potent purinergic receptor in normal BDE. Luminometry and bioassaying measured physiologically relevant levels of ATP in a subset of liver cyst fluid samples. Liver cyst epithelia also displayed a significant capacity to degrade extracellular ATP. In conclusion, regulated ion transport pathways are present in liver cyst epithelia and are positioned to direct fluid secretion into the lumen of liver cysts and promote increases in liver cyst expansion and growth.
AB - Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl- secretion and Na+ absorption. Na+ absorption was amiloride-sensitive, suggesting the activation of epithelial sodium channels (ENaC). Further, both cAMPi and extracellular ATP induced robust secretory responses. Western blotting and immunohistologic analysis of liver cyst epithelia demonstrated expression of P2X4, a potent purinergic receptor in normal BDE. Luminometry and bioassaying measured physiologically relevant levels of ATP in a subset of liver cyst fluid samples. Liver cyst epithelia also displayed a significant capacity to degrade extracellular ATP. In conclusion, regulated ion transport pathways are present in liver cyst epithelia and are positioned to direct fluid secretion into the lumen of liver cysts and promote increases in liver cyst expansion and growth.
KW - Autosomal dominant polycystic kidney disease (ADPKD)
KW - Epithelial sodium channel
KW - Purinergic signaling
KW - Ussing analysis
KW - cAMP
UR - http://www.scopus.com/inward/record.url?scp=33847044750&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847044750&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2006.11.006
DO - 10.1016/j.bbadis.2006.11.006
M3 - Article
C2 - 17208416
AN - SCOPUS:33847044750
SN - 0925-4439
VL - 1772
SP - 345
EP - 354
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 3
ER -