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Deletion of claudin‐7 in renal collecting duct cells impairs paracellular chloride permeability
Author(s) -
Fan Junming,
Tatum Rodney,
Hoggard John,
Jeansonne Beverly G,
Chen YanHua
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1148.16
Subject(s) - paracellular transport , claudin , endocrinology , permeability (electromagnetism) , medicine , chemistry , tight junction , biochemistry , membrane
We have reported previously that claudin‐7 knockout mice ( Cldn7 −/− ) display severe salt wasting and chronic dehydration phenotypes. To investigate the role of claudin‐7 in ion permeability in renal epithelial cells, we generated stable collecting duct (CD) cell lines isolated from Cldn7 +/+ and Cldn7 −/− mouse kidneys. Deletion of claudin‐7 significantly increased the transepithelial electrical resistance (TER) and decreased the absolute permeability for Cl − (P Cl ) and Na + (P Na ). The ratio of P Cl /P Na was <1, suggesting an impairment of Cl − permeability along with a suppression of Na + permeability in Cldn7 −/− CD cells. TER and dilution potential values were unchanged after inhibition of Cl − and Na + channels and the current‐voltage curves were linear in Cldn7 +/+ and Cldn7 −/− CD cells, indicating that the resulting ionic flux changes were through the paracellular pathway. The impairment of paracellular Cl − permeability can be rescued by transfecting Cldn7 −/− CD cells with claudin‐7 cDNA. In addition, we also found that the expression level of WNK4 was dramatically reduced in Cldn7 −/− CD cells, which was consistent with our previous finding that claudin‐7 is a substrate of WNK4 and can be phosphorylated by WNK4. Collectively, our findings indicate that deletion of claudin‐7 in CD cells impairs Cl − permeability, and that claudin‐7 could be one of the key factors in WNK4 mutations‐induced hypertension. This research is supported by NIH grant HL085752.