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Na+- K+- 2Cl¯ cotransporter (apical membrane)

 

Na+-K+-2Cl¯ cotransporters are a central component in the process of vectorial Na+ and Cl¯ transport in many secretory and absorptive epithelia.  Two isoforms have been identified (NKCC1 and NKCC2) which belong to the cation-Cl cotransporters (CCC) family of transporters.  

NKCC1 is widely expressed and is found in many types of cell.  It plays an important role in cell volume regulation as well as transepithelial ion transport.  In contrast, NKCC2 is expressed only in the thick ascending limb of loop of Henle (Russell, 2000).

 

NKCC1 in CSF secretion

 Recent evidence suggests that this transporter is expressed in the rat lateral and fourth ventricle choroid plexus (Bairmian et al., 1991; Keep et al., 1994).   Plotkin et al.(1997) demonstrated the expression of NKCC1 in the choroid plexus using in situ hybridization and western analysis.  Furthermore, Plotkin et al found that NKCC1 was localized on the apical membrane of epithelial cells.  The role of the transporter is unclear, i.e. does it mediate Cl¯ influx or efflux?  This is mainly due to the lack of definitive data on the ion gradients across the apical membrane.  Pathological changes have been observed in choroid plescus from NKCC1 "Knock-out" mice (Flagella et all, 1999).

        

 

             References

   Bairamian, D., Johanson, C. E., Prmalee, J. T. & Epstein, M. H. (1991). Pottasium cotransport with sodium and chloride in the choroid plexus. J. Neurochem. 56: 1629-1632.

   Flagella, M., Clarke, L.L., Miller, M.L. etal (1999). Mice lacking the basolateral Na - K - 2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J. Biol. Chem. 274: 26946 - 26955.

   Keep, R. F., Xiang, J. & Betz, A. L. (1994). Pottasium cotransport at the rat choroid plexus. Am. J. Physiol. 267: C1616-C1622.

   Plotkin, M. D., Kaplan, M. R., Peterson, L. N., Gullans, S. R., Hebert, S. C. & Delpire, E. (1997). Expression of the Na¯K¯2Cl cotransporter BSC2 in the nervous system. Am. J. Physiol. 272: C173-C183.

   Russell, J. M. (2000). Sodium-potassium-chloride cotransport. Physiol. Rev. 80: 211-276.

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