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The Journal of Neuroscience, April 1, 1998, 18(7):2506-2519
Aquaporin-4 Water Channel Protein in the Rat Retina and Optic
Nerve: Polarized Expression in Müller Cells and Fibrous
Astrocytes
Erlend A.
Nagelhus1,
Margaret L.
Veruki2,
Reidun
Torp1,
Finn-M.
Haug1,
Jon H.
Laake1,
Søren
Nielsen3,
Peter
Agre4, and
Ole P.
Ottersen1
Departments of 1 Anatomy and
2 Neurophysiology, Institute of Basic Medical Sciences,
University of Oslo, N-0317 Oslo, Norway, 3 Department of
Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000
Aarhus, Denmark, and 4 Departments of Biological Chemistry
and Medicine, The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205
The water permeability of cell membranes differs by orders of
magnitude, and most of this variability reflects the differential expression of aquaporin water channels. We have recently found that the
CNS contains a member of the aquaporin family, aquaporin-4 (AQP4). As a
prerequisite for understanding the cellular handling of water during
neuronal activity, we have investigated the cellular and subcellular
expression of AQP4 in the retina and optic nerve where
activity-dependent ion fluxes have been studied in detail. In
situ hybridization with digoxigenin-labeled riboprobes and immunogold labeling by a sensitive postembedding procedure demonstrated that AQP4 and AQP4 mRNA were restricted to glial cells, including Müller cells in the retina and fibrous astrocytes in the optic nerve. A quantitative immunogold analysis of the Müller cells showed that these cells exhibited three distinct membrane compartments with regard to AQP4 expression. End feet membranes (facing the vitreous
body or blood vessels) were 10-15 times more intensely labeled than
non-end feet membranes, whereas microvilli were devoid of AQP4. These
data suggest that Müller cells play a prominent role in the water
handling in the retina and that they direct osmotically driven water
flux to the vitreous body and vessels rather than to the subretinal
space. Fibrous astrocytes in the optic nerve similarly displayed a
differential compartmentation of AQP4. The highest expression of AQP4
occurred in end feet membranes, whereas the membrane domain facing the
nodal axolemma was associated with a lower level of immunoreactivity
than the rest of the membrane. This arrangement may allow transcellular
water redistribution to occur without inducing inappropriate volume
changes in the perinodal extracellular space.
Key words:
aquaporin; water homeostasis; potassium buffering; Müller cells; fibrous astrocytes; retina
Copyright © 1998 Society for Neuroscience 0270-6474/98/1872506-14$05.00/0
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