Chronic hypoxia enhances the secretory response of rat phaeochromocytoma cells to acute hypoxia

Open Access
Publisher Website
Google Scholar
Abstract
1 Amperometric recordings were made from individual phaeochromocytoma (PC12) cells using carbon fibre microelectrodes to investigate the effects of chronic hypoxia (10% O2) on the secretory responses evoked by acute hypoxia. 2 Exposure to chronic hypoxia for 21–26 h increased the frequency of exocytotic events evoked in response to acute hypoxia (Pca 10–60 mmHg). 3 Chronic hypoxia increased the value of Q1/3, determined by the integration of amperometric events, indicating an increase in quantal size: this reflects either an increase in vesicular dimensions or vesicular catecholamine concentration. 4 Exocytotic frequency evoked by bath application of tetraethylammonium (1–10 mm) was significantly enhanced following chronic hypoxia. 5 In both control and chronically hypoxic PC12 cells, exocytosis in response to acute hypoxia was completely abolished in Ca2+‐free solutions. Cd2+ (200 μm) completely inhibited exocytosis from control cells, but left a significant residual release in chronically hypoxic PC12 cells. 6 The Cd2+‐resistant release evoked by acute hypoxia in chronically hypoxic PC12 cells was inhibited by inorganic ions (0.01–10 mm) in a potency order of La3+ > Gd3+ > Zn2+. Ni2+ (10 mm) was without effect. 7 Our results suggest that chronic hypoxia enhances the secretory response of PC12 cells in part by increasing the depolarization mediated by an oxygen‐sensitive K+ channel. In addition, acute hypoxia activates a Cd2+‐resistant Ca2+ influx pathway in chronically hypoxic PC12 cells.