Abstract：
:Tight junction (TJ) properties are determined by membrane protein complexes of neighboring cells that form both a barrier and a selective pathway for paracellular substrate transport. Our previous work supports the view that paracellular permeability changes in the thick ascending limb (TAL) may underlie the mechanism for familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), a rare autosomal recessive disease linked to mutations in claudin-16 (CLDN16) and claudin-19 (CLDN19). CLDN16 knockdown (KD) mice are lacking CLDN16 expression by transgenic RNA interference. We observed that the transport defect for Mg(2+) and Ca(2+) in this animal model is caused by a loss of paracellular cation selectivity. The permeability ratio for Na(+) over Cl(-) in KD mice was lower by a factor of two without a change in paracellular conductance, compared to wild type (WT). This resulted in a collapse of the transepithelial voltage, which is the driving force for Mg(2+) and Ca(2+) absorption in TAL. Since CLDN16 KD mice revealed lower blood pressure and an increased aldosterone plasma concentration, we hypothesize that the reduction in paracellular selectivity could allow backflow of Na(+) and Cl(-) into the lumen of the TAL, thus enhancing the distal NaCl load and challenging the organism with a latent NaCl loss.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Shan Q,Himmerkus N,Hou J,Goodenough DA,Bleich Mdoi
10.1111/j.1749-6632.2009.04041.xsubject
Has Abstractpub_date
2009-05-01 00:00:00pages
148-51eissn
0077-8923issn
1749-6632pii
NYAS04041journal_volume
1165pub_type
杂志文章abstract：:The slowpoke gene of Drosophila melanogaster encodes a Ca-activated K channel. This gene is expressed in neurons, muscles, tracheal cells, and the copper and iron cells of the midgut. The gene produces a large number of alternative products using tissue-specific transcriptional promoters and alternative mRNA splicing....
journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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更新日期：2009-03-01 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：2010-01-01 00:00:00
