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Gene Review

Aqp4  -  aquaporin 4

Rattus norvegicus

Synonyms: AQP-4, Aquaporin-4, MIWC, MIWC2, Mercurial-insensitive water channel, ...
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Disease relevance of Aqp4

  • In response to dehydration (3 days, -15 % body weight), renal expression of CHIP28 and MIWC were unchanged, whereas expression of AQP-CD and GLIP were increased significantly by 2.18 +/- 0.04 and 1.36 +/- 0.11 fold (SE, n = 5), respectively [1].
  • CONCLUSIONS: Cerebral cortical AQP4 expression is up-regulated after normothermic CA, which is attenuated by hypothermia induced before CA [2].
  • Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats [2].
  • Down-regulated AQP4 mRNA expression may be one of the molecular mechanisms maintaining water homeostasis in diffusely injured brain exposed to acute hyponatremia [3].
  • Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats [4].

High impact information on Aqp4

  • Perivascular astrocyte end-feet contain distinctive orthogonal lattices (square arrays) assembled from 4- to 6-nm intramembrane particles (IMPs) corresponding to individual AQP4 tetramers [5].
  • Osmotic homeostasis in the brain involves movement of water through aquaporin-4 (AQP4) membrane channels [5].
  • Two isoforms of AQP4 result from translation initiation at methionine residues M1 and M23, but no functional differences are known [5].
  • Immunocytochemical analysis of the brain recently revealed that AQP4 has a highly polarized distribution, with marked expression in astrocyte end-feet that surround capillaries and form the glia limitans; however, the structural organization of AQP4 has remained unknown [6].
  • Based on this evidence that AQP4 is concentrated in glial square arrays, freeze-fracture methods may now provide biophysical insights regarding neuropathological states in which abnormal fluid shifts are accompanied by alterations in the aggregation state or the molecular architecture of square arrays [6].

Chemical compound and disease context of Aqp4


Biological context of Aqp4


Anatomical context of Aqp4

  • To determine whether astrocyte and ependymocyte square arrays contain AQP4, we employed immunogold labeling of SDS-washed freeze-fracture replicas and stereoscopic confirmation of tissue binding [6].
  • By in situ hybridization, MIWC showed an unique distribution in cells that do not express CHIP28, including kidney papillary vasa recta, cells lining the subarachnoid space and ventricles in brain, the inner nuclear layer in retina, and the conjunctival epithelium [11].
  • Water permeability was strongly increased in Xenopus oocytes expressing MIWC in a mercurial-insensitive manner, in contrast to known water channels [11].
  • The MIWC water channel may participate in the urinary concentrating mechanism, the absorption of cerebrospinal fluid, and other physiological processes [11].
  • MIWC mRNA expression was highest in brain, followed by eye, trachea, lung, stomach, kidney, and skeletal muscle [1].

Associations of Aqp4 with chemical compounds

  • On the other hand, in the CHG group, expression of AQP-1 and AQP-4 were significantly suppressed, and ultrafiltration volume was lost [13].
  • The use of PSL with CHG completely restored the expression of AQP-1 and AQP-4, and peritoneal function improved [13].
  • In contrast, AQP4 mRNA is strongly expressed in astrocytes, but no expression is found in primary or passaged brain microvessel endothelial cells, or in RBE4 or C6 cells [16].
  • There were no significant changes in aquaporin-1, aquaporin-4, or urea transporters [17].
  • Exposure to ambient 21% O2 may contribute to increases in AQP-4 and ENaC expression to facilitate water transport across neonatal airway epithelia in the immediate postnatal period [18].

Regulatory relationships of Aqp4


Other interactions of Aqp4

  • In contrast, the abundance of whole kidney AQP1 (90 +/- 3%) and inner medullary AQP4 (121 +/- 16%) was unchanged in rats with DM [12].
  • No effect of mbetaCD treatment on the basolateral distribution of AQP3 and AQP4 was detected [21].
  • Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2 [22].
  • Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau [23].
  • Thus, we investigated the expression, subcellular localization, possible regulation by secretin, and functional activity of AQP4, a mercury-insensitive water channel expressed in other fluid transporting epithelia [24].

Analytical, diagnostic and therapeutic context of Aqp4


  1. Quantitative analysis of aquaporin mRNA expression in rat tissues by RNase protection assay. Umenishi, F., Verkman, A.S., Gropper, M.A. DNA Cell Biol. (1996) [Pubmed]
  2. Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats. Xiao, F., Arnold, T.C., Zhang, S., Brown, C., Alexander, J.S., Carden, D.L., Conrad, S.A. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. (2004) [Pubmed]
  3. Impact of experimental acute hyponatremia on severe traumatic brain injury in rats: influences on injuries, permeability of blood-brain barrier, ultrastructural features, and aquaporin-4 expression. Ke, C., Poon, W.S., Ng, H.K., Lai, F.M., Tang, N.L., Pang, J.C. Exp. Neurol. (2002) [Pubmed]
  4. Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats. Kiening, K.L., van Landeghem, F.K., Schreiber, S., Thomale, U.W., von Deimling, A., Unterberg, A.W., Stover, J.F. Neurosci. Lett. (2002) [Pubmed]
  5. Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms. Furman, C.S., Gorelick-Feldman, D.A., Davidson, K.G., Yasumura, T., Neely, J.D., Agre, P., Rash, J.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Rash, J.E., Yasumura, T., Hudson, C.S., Agre, P., Nielsen, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Active water selective channels in the stomach: investigation of aquaporins after ethanol and capsaicin treatment in rats. Bódis, B., Nagy, G., Németh, P., Mózsik, G. J. Physiol. Paris (2001) [Pubmed]
  8. Testosterone up-regulates aquaporin-4 expression in cultured astrocytes. Gu, F., Hata, R., Toku, K., Yang, L., Ma, Y.J., Maeda, N., Sakanaka, M., Tanaka, J. J. Neurosci. Res. (2003) [Pubmed]
  9. Sulforaphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury. Zhao, J., Moore, A.N., Clifton, G.L., Dash, P.K. J. Neurosci. Res. (2005) [Pubmed]
  10. Ifenprodil treatment is associated with a down-regulation of brain aquaporin 4 following cardiac arrest in rats. Xiao, F., Pardue, S., Arnold, T.C., Monroe, J., Alexander, J.S., Carden, D.L., Turnage, R., Conrad, S.A. Acta Neurochir. Suppl. (2005) [Pubmed]
  11. Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. Hasegawa, H., Ma, T., Skach, W., Matthay, M.A., Verkman, A.S. J. Biol. Chem. (1994) [Pubmed]
  12. Compensatory increase in AQP2, p-AQP2, and AQP3 expression in rats with diabetes mellitus. Nejsum, L.N., Kwon, T.H., Marples, D., Flyvbjerg, A., Knepper, M.A., Frøkiaer, J., Nielsen, S. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  13. Glucocorticoid restores the deterioration of water transport in the peritoneum through increment in aquaporin. Imai, H., Nakamoto, H., Ishida, Y., Inoue, T., Kanno, Y., Okada, H., Suzuki, S., Okano, H., Suzuki, H. Advances in peritoneal dialysis. Conference on Peritoneal Dialysis. (2000) [Pubmed]
  14. Select types of supporting cell in the inner ear express aquaporin-4 water channel protein. Takumi, Y., Nagelhus, E.A., Eidet, J., Matsubara, A., Usami, S., Shinkawa, H., Nielsen, S., Ottersen, O.P. Eur. J. Neurosci. (1998) [Pubmed]
  15. Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. Frigeri, A., Gropper, M.A., Turck, C.W., Verkman, A.S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  16. Induction of aquaporin 1 but not aquaporin 4 messenger RNA in rat primary brain microvessel endothelial cells in culture. Dolman, D., Drndarski, S., Abbott, N.J., Rattray, M. J. Neurochem. (2005) [Pubmed]
  17. Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat. Ohara, M., Cadnapaphornchai, M.A., Summer, S.N., Falk, S., Yang, J., Togawa, T., Schrier, R.W. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Modulation of aquaporin 4 and the amiloride-inhibitable sodium channel in perinatal rat lung epithelial cells. Ruddy, M.K., Drazen, J.M., Pitkanen, O.M., Rafii, B., O'Brodovich, H.M., Harris, H.W. Am. J. Physiol. (1998) [Pubmed]
  19. Expression of aquaporins in the rat ocular tissue. Patil, R.V., Saito, I., Yang, X., Wax, M.B. Exp. Eye Res. (1997) [Pubmed]
  20. Expression and localization of aquaporins in rat gastrointestinal tract. Koyama, Y., Yamamoto, T., Tani, T., Nihei, K., Kondo, D., Funaki, H., Yaoita, E., Kawasaki, K., Sato, N., Hatakeyama, K., Kihara, I. Am. J. Physiol. (1999) [Pubmed]
  21. Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney. Russo, L.M., McKee, M., Brown, D. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  22. Downregulation of renal aquaporins in response to unilateral ureteral obstruction. Li, C., Wang, W., Knepper, M.A., Nielsen, S., Frøkiaer, J. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  23. Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau. Bobik, M., Ellisman, M.H., Rudy, B., Martone, M.E. Brain Res. (2004) [Pubmed]
  24. Expression of aquaporin-4 water channels in rat cholangiocytes. Marinelli, R.A., Pham, L.D., Tietz, P.S., LaRusso, N.F. Hepatology (2000) [Pubmed]
  25. Expression of aquaporin 1 and aquaporin 4 water channels in rat choroid plexus. Speake, T., Freeman, L.J., Brown, P.D. Biochim. Biophys. Acta (2003) [Pubmed]
  26. Distribution of aquaporin-4 water channel expression within rat kidney. Terris, J., Ecelbarger, C.A., Marples, D., Knepper, M.A., Nielsen, S. Am. J. Physiol. (1995) [Pubmed]
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