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WATER AND ELECTROLYTE HOMEOSTASIS

Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain

¹Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut; ²Department of Physiology, Emory University, Atlanta, Georgia; ³Departments of Pediatrics and ⁴Neuroscience, University of California San Diego, La Jolla, California; and ⁵The Rady Children's Hospital, San Diego, California

Submitted 10 July 2007 ; accepted in final form 3 October 2007

In the mammalian CNS, hypoxia causes a wide range of physiological effects, and these effects often depend on the stage of development. Among the effects are alterations in pH homeostasis. Na⁺-coupled HCO₃^– transporters can play critical roles in intracellular pH regulation and several, such as NCBE and NBCn1, are expressed abundantly in the central nervous system. In the present study, we examined the effect of chronic continuous hypoxia on the expression of two electroneutral Na-coupled HCO₃^– transporters, SLC4a7 (NBCn1) and SLC4a10 (NCBE), in mouse brain, the first such study on any acid-base transporter. We placed the mice in normobaric chambers and either maintained normoxia (21% inspired O₂) or imposed continuous chronic hypoxia (11% O₂) for a duration of either 14 days or 28 days, starting from ages of either postnatal age 2 days (P2) or P90. We assessed protein abundance by Western blot analysis, loading equal amounts of total protein for each condition. In most cases, hypoxia reduced NBCn1 levels by 20–50%, and NCBE levels by 15–40% in cerebral cortex, subcortex, cerebellum, and hippocampus, both after 14 and 28 days, and in both pups and adults. We hypothesize that these decreases, which are out of proportion to the expected overall decreases in brain protein levels, may especially be important for reducing energy consumption.

electroneutral; bicarbonate transporter; SLC4; central nervous system

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