Immunocytochemical studies of aquaporin 4, Kir4.1, and α1-syntrophin in the astrocyte endfeet of mouse brain capillaries.
One of the most important physiological roles of brain astrocytes is the maintenance of extracellular K(+) concentration by adjusting the K(+) influx and K(+) efflux. The inwardly rectifying K(+) channel Kir4.1 has been identified as an important member of K(+) channels and is highly concentrated in glial endfeet membranes. Aquaporin (AQP) 4 is another abundantly expressed molecule in astrocyte endfeet membranes. We examined the ultrastructural localization of Kir4.1, AQP4, α1-syntrophin, and β-spectrin molecules to understand the functional role(s) of Kir4.1 and AQP4. Immunogold electron microscopy of these molecules showed that the signals of these molecules were present along the plasma membranes of astrocyte endfeet. Double immunogold electron microscopy showed frequent co-localization in the combination of molecules of Kir4.1 and AQP4, Kir4.1 and α1-syntrophin, and AQP4 and α1-syntrophin, but not those of AQP4 and β-spectrin. Our results support biochemical evidence that both Kir4.1 and AQP4 are associated with α1-syntrophin by way of postsynaptic density-95, Drosophila disc large protein, and the Zona occludens protein I protein-interaction domain. Co-localization of AQP4 and Kir4.1 may indicate that water flux mediated by AQP4 is associated with K(+) siphoning.
Masaki
Hisatsugu
H
Department of Neurology, Showa University Fujigaoka Hospital.
Wakayama
Yoshihiro
Y
Hara
Hajime
H
Jimi
Takahiro
T
Unaki
Akihiko
A
Iijima
Shoji
S
Oniki
Hiroaki
H
Nakano
Kiyoko
K
Kishimoto
Koji
K
Hirayama
Yoshiko
Y
Glia. 2001 Jan;33(1):57-71
11169792
Arch Neurol. 2002 Mar;59(3):431-7
11890849
Glia. 2002 Sep;39(3):292-303
12203395
Exp Brain Res. 1980;40(4):432-9
6254790
J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):262-5
11796780
Glia. 2000 Jun;30(4):362-72
10797616
Cell Tissue Res. 2003 Feb;311(2):131-8
12596033
Acta Neuropathol. 1997 Nov;94(5):455-64
9386778
J Neurosci. 1997 Jan 1;17(1):171-80
8987746
J Clin Invest. 1999 Mar;103(6):767-72
10079096
J Biol Chem. 2004 Jul 2;279(27):28387-92
15102837
J Neurosci. 1997 Oct 15;17(20):7725-35
9315894
J Neurosci. 2000 Aug 1;20(15):5733-40
10908613
J Neurosci. 1985 Feb;5(2):532-5
3973681
Glia. 2004 Aug 1;47(2):138-49
15185393
J Cell Biol. 2001 Oct 1;155(1):113-22
11571312
Neuroscience. 2004;129(4):905-13
15561407
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2106-11
12578959
J Biol Chem. 1994 Feb 25;269(8):5497-500
7509789
Am J Physiol Cell Physiol. 2001 Sep;281(3):C922-31
11502569
Glia. 1999 Mar;26(1):47-54
10088671
Acta Neuropathol. 2005 Apr;109(4):418-26
15723236
Science. 1984 Sep 14;225(4667):1174-5
6474173
J Biol Chem. 1994 Feb 25;269(8):6040-4
8119949