Hypoxia evokes catecholamine secretion from rat pheochromocytoma PC-12 cells

Biochem Biophys Res Commun. 1998 Jul 9;248(1):13-7. doi: 10.1006/bbrc.1998.8905.


We have monitored exocytosis of catecholamines from individual PC-12 cells by amperometry using carbon fiber microelectrodes in order to investigate possible secretory responses to acute hypoxia. In normoxia, no secretion was detected from cells perfused with a solution containing 5 mM K+. However, when [K+] was raised (10-100 mM), exocytotic events were observed. Hypoxia (PO2 11 mmHg) stimulated secretion from PC-12 cells, and in hypoxic conditions exocytosis was greater at each [K+] studied as compared with normoxia. Hypoxia-evoked secretion was abolished in Ca2+ free solutions containing 1 mM EGTA and by the non-specific Ca2+ channel blocker, Cd2+ (200 microM). Secretion was also largely inhibited by omega-conotoxin GVIA (1 microM). Exocytosis was also observed in normoxia when cells were exposed to tetraethylammonium (1-10 mM), but not 4-aminopyridine (3 mM). Our findings indicate that hypoxia evokes exocytosis via depolarization arising from inhibition of a TEA-sensitive K+ conductance, leading to Ca2+ influx primarily via N-type Ca2+ channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Catecholamines / metabolism*
  • Cell Hypoxia / physiology*
  • Exocytosis* / drug effects
  • Nifedipine / pharmacology
  • PC12 Cells
  • Peptides / pharmacology
  • Potassium / metabolism
  • Rats
  • Spider Venoms / pharmacology
  • Tetraethylammonium / pharmacology
  • omega-Agatoxin IVA
  • omega-Conotoxin GVIA


  • Calcium Channel Blockers
  • Calcium Channels
  • Catecholamines
  • Peptides
  • Spider Venoms
  • omega-Agatoxin IVA
  • Cadmium
  • Tetraethylammonium
  • omega-Conotoxin GVIA
  • Nifedipine
  • Potassium
  • Calcium