The electroneutral Na⁺-K⁺-2Cl^– cotransporters are expressed in a wide variety of epithelial and non-epithelial tissues. Two distinct isoforms (NKKC1 and NKCC2) have been identified to date. NKCC1 is located predominantly in the basolateral membrane of epithelia, where it is involved in fluid secretory processes. Since NKCC1 was first cloned from the shark rectal gland (Xu et al. 1994), Northern blot analysis has also localised this isoform in tissues as diverse as the kidney, stomach, lung, heart, skeletal muscle and neurones. However, it is only recently, since the development of the targeted gene disruption technique, that we have begun to fully understand the functional role of this important transport protein (Delpire & Mount, 2002). My presentation will discuss recent insights into the physiological role and pathophysiological consequences of disruption of the Nkcc1 gene, with particular reference to the effects on inner ear function (Delpire et al. 1999), and salivary gland secretion (Evans et al. 2000).

This work was supported by National Institutes of Health Grants DE13539, DE08921 and DE09692 to Prof. J. E. Melvin.

Author’s present address: Unilever Research & Development, Port Sunlight Laboratory, Bebington, Wirral CH63 3JW, UK.