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Loss of Primary Cilia Induces the Appearance of a Non‐Selective Cation Channel in the Apical Membrane of Mouse CCD Principal Cells
Author(s) -
Saigusa Takamitsu,
Yue Qiang,
Thai Tiffany,
Bell P.Darwin,
Eaton Douglas
Publication year - 2015
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.29.1_supplement.663.4
Subject(s) - cilium , apical membrane , polycystic kidney disease , microbiology and biotechnology , cholangiocyte , biology , membrane potential , duct (anatomy) , chemistry , medicine , endocrinology , anatomy , epithelium , kidney , biophysics , genetics
Polycystic kidney disease (PKD) is a ciliopathic disorder, which produces gross abnormalities in the kidney, making the initial events in the disease difficult to study. Cysts in PKD arises mostly from the collecting duct, but the mechanism by which cilia promotes cyst formation is unknown. We used adult Ift88 (cilia) conditional knockout mouse, an autosomal recessive PKD model, with or without tamoxifen inducible Cre. Two weeks after inducing Cre, we examined the effects of ciliary loss on single channels in the apical membranes of principal cells of isolated, spit open CCDs in 17 Cre + and 24 Cre ‐ tubules (8 mice each). 4 Cre + and 11 Cre ‐ tubules had measurable channel activity. Channels in Cre ‐ mice were all 5pS Na + selective channels with long mean open times (475.7 ± 83.26 ms) and P o greater than 0.2 very similar to previously reported ENaC channels. Cre + principal cells had two types of channels. One cell had an ENaC‐like channel, but all of the cells had 21 pS non‐selective cation channels (reversal potential near zero) with short mean open times (72 ± 17 ms) an open probability <0.08 and a characteristic flickery opening. This is similar to the previous reported 23 pS non‐selective cation channel (NSC) seen in a collecting duct cell line derived from mouse of Ift88 hypomorph (PLoS One. 2013; 8(8): e73424). We interpret these results to imply that an early event in ciliary loss is the induction of a NSC channel at the apical membrane. Whether this channel is the same as the TRPV4/polycystin 2 channel that was identified in cell culture remains to be determined.