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Altered Regulation of Ion Channel Activity by EGF in Polycystic Kidney Disease
Author(s) -
Zhang ZhiRen,
Chu WenFeng,
Komlosi Peter,
Haycraft Courtney J.,
Bell Phillip Darwin
Publication year - 2008
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.22.1_supplement.1158.19
Subject(s) - cilium , microbiology and biotechnology , ion channel , chemistry , epidermal growth factor , biophysics , patch clamp , receptor , biology , medicine , biochemistry
Cilia are responsible for fluid flow‐induced increases in [Ca 2+ ] i and that this increase in [Ca 2+ ] i may be mediated by member(s) of the transient receptor potential channel family. To elucidate whether there are different cellular ion channel activities in orpk cilia (−) and orpk cilia (+) collecting duct cell lines, derived from the Tg737 orpk mouse, we performed single‐channel patch‐clamp recordings in these cells. We observed channels in both cell types having a conductance of ~23 pS but with a different rate of occurrence; channels were observed in 64% of patches from cilia (−) cells vs. 35% of patches from cilia (+) cells. Results of ion selectivity experiments suggest that a non‐selective cation channel mediates these currents. These channels are regulated by epidermal growth factor (EGF). In cilia (−) cells, channel activity was markedly up‐regulated by apical application of EGF. In contrast, channel activity in cilia (+) cells was enhanced by EGF applied only to the basolateral membrane. These results suggest that EGF‐dependent signaling contributes to the regulation of non‐selective cation channels in these cells. Thus, defective cilia structure/function leads to increased apical non‐selective cation channel activity and alterations in membrane coupling to and enhanced sensitivity of this channel to EGF receptor activation.