Date of Completion

Spring 5-6-2012

Thesis Advisor(s)

J. Larry Renfro

Department

Physiology and Neurobiology

Disciplines

Molecular and Cellular Neuroscience | Other Neuroscience and Neurobiology | Physiology

Abstract

: A major function of the brain choroid plexus (CP) is to regulate the exchange of solutes between the blood plasma and the cerebrospinal fluid (CSF) using selective transporters. CSF inorganic phosphate (Pi) concentration is maintained at about one-half that of plasma and is potentially important because of its regulatory, structural, and biochemical functions. Phosphate is critical for ATP and DNA formation, the linked regulation between phosphate and calcium, and as an intracellular buffer. The human body has two major Pi transporter gene families known as SLC34 (NaPi-II) and SLC20 (PiT), which have wide tissue distribution. Although both families are secondary-active and sodium-dependent, they are distinguished by their transport mechanisms and functional properties. NaPi-II-type and PiT-type transporters are characterized by their substrate stoichiometry and inhibition profile. Unlike NaPi-II-type transporters, PiT-type transporters are not inhibited by phosphonoformic acid (PFA) and can partially substitute Li+ for Na+. Bataille et al. (unpublished) used these differences to characterize the effects of arsenate, PFA, and Li+ on CP phosphate transport. The results indicate that a PiT-type transporter is responsible for Pi transport in the CP. To further support this hypothesis, RT-PCR and western blotting were performed to definitively determine if NaPi-II-type transporters are present or absent from the CP. The results confirm the presence of PiT-like transporters but also indicate that NaPi-IIb is potentially present in the CP. Thus, the secondary-active, CP transport of phosphate out of the CSF may involve more than one family of solute carrier transporters.