Introduction

The blood–brain barrier (BBB), formed by the cerebral endothelial cells and their connecting tight junctions, has a very low permeability to ions unless specific transporters are present. The endothelial movement of ions, via either ion transporters or ion channels, has a number of important functions. It is involved in the regulation of several key ion concentrations in the brain (e.g. K+, Ca2+, H+), the uptake and extrusion of trace metals, fluid secretion and, by linkage to the endothelial sodium gradient, nutrient transport. Ion transport is also important in regulating BBB function. For example, changes in endothelial cell [Ca2+] and volume modulate BBB integrity (Rapoport et al., 1980; Olesen and Crone, 1986).

Understanding ion transport at the BBB may aid in the treatment of a number of disease states, particularly those such as stroke where edema formation results from a net accumulation of ions and thus water in the brain (Betz et al., 1994). However, despite the importance of BBB ion transport in normal and pathophysiological conditions and its potential for modulating BBB function, our knowledge of ion transport and its regulation is still far from complete. This particularly reflects the limitations of in vivo BBB experimentation and deficiencies in current in vitro preparations. Although such difficulties apply to all studies of the BBB, they are particularly pertinent to ion transport because of the low rate of transport.