Ion permeability profiles of renal paracellular channel-forming claudins.

Aim: Members of the claudin protein family are the major constituents of tight junction strands and determine the permeability properties of the paracellular pathway. In the kidney, each nephron segment expresses a distinct subset of claudins that form either barriers against paracellular solute transport or charge- and size-selective paracellular channels. It was the aim of the present study to determine and compare the permeation properties of these renal paracellular ion channel-forming claudins.

Methods: MDCK II cells, in which the five major claudins had been knocked out (claudin quintupleKO), were stably transfected with individual mouse Cldn2, -4, -8, -10a, -10b, or -15, or with dog Cldn16 or -19, or with a combination of mouse Cldn4 and Cldn8, or dog Cldn16 and Cldn19. Permeation properties were investigated in the Ussing chamber and claudin interactions by FRET assays.

Results: Claudin-4 and -19 formed barriers against solute permeation. However, at low pH values and in the absence of HCO , claudin-4 conveyed a weak chloride and nitrate permeability. Claudin-8 needed claudin-4 for assembly into TJ strands and abolished this anion preference. Claudin-2, -10a, -10b, -15, -16+19 formed highly permeable channels with distinctive permeation profiles for different monovalent and divalent anions or cations, but barriers against the permeation of ions of opposite charge and of the paracellular tracer fluorescein.

Conclusion: Paracellular ion permeabilities along the nephron are strictly determined by claudin expression patterns. Paracellular channel-forming claudins are specific for certain ions and thus lower transepithelial resistance, yet form barriers against the transport of other solutes.