title: Chronic hypoxia enhances the secretory response of rat phaeochromocytoma cells to acute hypoxia.
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 (PO2 ca 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 microM) 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.
authors.affiliation: Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Peers
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000503:physiopathology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D004594:Electrophysiology; D005089:Exocytosis; D007700:Kinetics; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D002412:Cations; D015221:Potassium Channels; D002104:Cadmium; D019789:Tetraethylammonium; D002118:Calcium