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

1. Amperometric recordings were made from individual phaeochromocytoma (PC1 2) cells using carbon fibre microelectrodes to investigate the effects of c hronic hypoxia (10% O-2) on the secretory responses evoked by acute hypoxia . 2. Exposure to chronic hypoxia for 21-26 h increased the frequency of exocy totic events evoked in response to acute hypoxia (P-O2 Ca 10-60 mmHg). 3. Chronic hypoxia increased the value of Q(1/3), determined by the integra tion of amperometric events, indicating an increase in quantal size: this r eflects either an increase in vesicular dimensions or vesicular catecholami ne 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 respon se to acute hypoxia was completely abolished in Ca2+-free solutions. Cd2+ ( 200 mu M) completely inhibited exocytosis from control cells, but left a si gnificant residual release in chronically hypoxic PC12 cells. 6. The Cd2+-resistant release evoked by acute hypoxia in chronically hypoxi c PC12 cells was inhibited by inorganic ions (0.01-10 mM) in a potency orde r of La3+ > Gd3+ > Zn2+. Ni2+ (10 mM) was without effect. 7. Our results suggest that chronic hypoxia enhances the secretary response of PC12 cells in part by increasing the depolarization mediated by an oxyg en-sensitive K+ channel. In addition, acute hypoxia activates a Cd2+-resist ant Ca2+ influx pathway in chronically hypoxic PC12 cells.