Chronic hypoxia inhibits Na+/Ca2+ exchanger expression in cortical astrocytes.

ABSTRACT

Ca signalling is central to many diverse functions of astrocytes. Of the numerous proteins involved in Ca homeostasis, the Na(+)/Ca(2+) exchanger is of particular importance in signalling regulation. We have shown that Ca signaling is dramatically remodelled in astrocytes by periods of chronic hypoxia, in part by inhibition of Na(+)/Ca(2+) exchanger. Here, we demonstrate that bepridil-sensitive Ca extrusion (indicative of Na(+)/Ca(2+) exchanger activity) is suppressed following 24 h hypoxia (2.5 or 1% O2) owing to a loss of Na(+)/Ca(2+) exchanger expression, as determined using immunocytochemistry and Western blots. Hypoxic Na(+)/Ca(2+) exchanger 1 inhibition occurs at the level of transcription, as mRNA for Na(+)/Ca(2+) exchanger 1 was significantly suppressed by hypoxia. Our results show hypoxia perturbs Ca homeostasis in astrocytes via the suppression of Na(+)/Ca(2+) exchanger 1 expression.