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Claudins, such as CLDN8, are components of epithelial cell tight junctions. Tight junctions regulate movement of solutes and ions through the paracellular space and prevent mixing of proteins and lipids in the outer leaflet of the apical and basolateral plasma membrane domains. Cldn8 expression reduced paracellular permeability to monovalent inorganic and organic cations and to divalent cations, but not to anions or neutral substrates. The results were consistent with a model in which CLDN2 encodes a highly cation-permeable channel, whereas CLDN8 acts primarily as a cation barrier. Cldn8 was expressed primarily at the tight junction along the entire aldosterone-sensitive distal nephron and in the late segments of the thin descending limbs of long-looped nephrons.
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