Abstract
Key points : It is a fundamental, yet unsolved physiological question how water transport is coupled to ion transport. Na+–K+–2Cl‐ cotransporters (NKCCs) play a fundamental role in cellular water and ion homeostasis. In epithelial cells the NKCC1 isoform is located unilaterally and plays a key role in secretory processes such as salivary production. The other isoform, NKCC2, is located primarily to kidney distal tubule where it is responsible for salt reabsorption. The present investigation shows that the NKCC1 isoform cotransports water together with the ions by a mechanism closely associated with the protein itself. In contrast the NKCC2 isoform transports ions but not water. Our data establish that coupling between salt and water transport takes place in certain cotransporters, for example NKCC1. Such proteins may constitute the link between the metabolic energy used by the Na+,K+‐ATPase, the cationic gradients established, and water transport.

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