Chronic hypoxia inhibits Na+/Ca2+ exchanger expression in cortical astrocytes.
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.
Atkinson
Lucy
L
Faculties of Medicine and Biological Sciences, University of Leeds, Leeds, UK.
Boyle
John P
JP
Pearson
Hugh A
HA
Peers
Chris
C
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015764:Bepridil / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D002121:Calcium Channel Blockers; D019831:Sodium-Calcium Exchanger; D015764:Bepridil; D001920:Bradykinin