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Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat

Xianghong Arakaki1, Paige McCleary1, Matthew Techy1, Jiarong Chiang1, Linus Kuo1, Alfred N Fonteh1, Brian Armstrong2, Dan Levy3 and Michael G Harrington1*

Author Affiliations

1 Molecular Neurology Program, Huntington Medical Research Institutes, 99 N. El Molino Avenue, Pasadena, CA, 91101, USA

2 Light Microscopy Core Facility, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

3 Headache Research Laboratory, Department of Anesthesia and Critical Care, Harvard Medical School, 330 Brookline Ave E/CLS 639, Boston, MA, 02115, USA

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Fluids and Barriers of the CNS 2013, 10:14  doi:10.1186/2045-8118-10-14

Published: 14 March 2013



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.


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.


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.


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.

Cerebrospinal fluid (CSF); Choroid plexus (CP); Meninges; Retina