| 要旨 |
Epithelial transport of ions and water is a prerequisite for whole body homeostasis. Any type of function, from systemic blood pressure control to cell excitability, requires the respective volume and its ion composition. The kidney tubular epithelium comprises the highest transport rates, followed by exocrine glands and the gastrointestinal tract. As ion transport consumes energy in a direct (pumps) or indirect (channels and carriers) fashion, evolution of the most cost-effective transport mechanism resulted in the combined use of transcellular and paracellular transport. Both transport pathways influence each other and are powered by electrochemical and osmotic gradients across the epithelium. The paracellular pathway is controlled by multi-protein complexes with claudin proteins as the key determinants of tight junction properties. These properties cover the whole range from barrier to conductivity and normally show ion selectivity. Also, epithelial water permeation depends completely on the composition of the tight junction and the adjacent cell membranes. The thick ascending limb of Henle is water tight, shows very high rates of NaCl transport and plays a key role in reabsorption of divalent cations. We have investigated this segment in detail by in vitro perfusion, imaging techniques, and molecular analysis. The data from control mice, claudin-10b conditional knockout and claudin-16 knockout mice help to decipher a more detailed understanding of TAL transport processes and the respective human disease in case of claudin mutations.
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