title: Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted.
  
  
  METHODS
  Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively.
  
  
  RESULTS
  The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier.
  
  
  CONCLUSIONS
  Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 N, El Molino Avenue, Pasadena, CA, 91101, USA. mghworks@hmri.org.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Arakaki
authors.forename: Paige
authors.initials: P
authors.lastname: McCleary
authors.forename: Matthew
authors.initials: M
authors.lastname: Techy
authors.forename: Jiarong
authors.initials: J
authors.lastname: Chiang
authors.forename: Linus
authors.initials: L
authors.lastname: Kuo
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.forename: Brian
authors.initials: B
authors.lastname: Armstrong
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington