Effects of chronic hypoxia on Ca2+ stores and capacitative Ca2+ entry in human neuroblastoma (SH‐SY5Y) cells

Microfluorimetric measurements of intracellular calcium ion concentration [Ca2+]i were employed to examine the effects of chronic hypoxia (2.5% O2, 24 h) on Ca2+ stores and capacitative Ca2+ entry in human neuroblastoma (SH‐SY5Y) cells. Activation of muscarinic receptors evoked rises in [Ca2+]i which were enhanced in chronically hypoxic cells. Transient rises of [Ca2+]i evoked in Ca2+‐free solutions were greater and decayed more slowly following exposure to chronic hypoxia. In control cells, these transient rises of [Ca2+]i were also enhanced and slowed by removal of external Na+, whereas the same manoeuvre did not affect responses in chronically hypoxic cells. Capacitative Ca2+ entry, observed when re‐applying Ca2+ following depletion of intracellular stores, was suppressed in chronically hypoxic cells. Western blots revealed that presenilin‐1 levels were unaffected by chronic hypoxia. Exposure of cells to amyloid β peptide (1–40) also increased transient [Ca2+]i rises, but did not mimic any other effects of chronic hypoxia. Our results indicate that chronic hypoxia causes increased filling of intracellular Ca2+ stores, suppressed expression or activity of Na+/Ca2+ exchange and reduced capacitative Ca2+ entry. These effects are not attributable to increased amyloid β peptide or presenilin‐1 levels, but are likely to be important in adaptive cellular remodelling in response to prolonged hypoxic or ischemic episodes.