1. Amperometric recordings were conducted to investigate the ability of hypoxia and anoxia to evoke quantal catecholamine secretion from isolated type I cells of the rat carotid body. 2. Hypoxia (P(O2) 8-14 mmHg) consistently failed to evoke catecholamine secretion from type I cells, when cells were perfused either at room temperature (21-24 degrees C) or at 35-37 degrees C, and regardless of whether Hepes- or HCO(3)(-)/CO(2)-buffered solutions were used. 3. Elevating extracellular [K(+)] caused concentration-dependent secretion from individual type I cells, with a threshold concentration of approximately 25 mM. In the presence of this level of extracellular K(+), hypoxia (P(O2) 8-14 mmHg) caused a marked enhancement of secretion which was fully blocked by 200 mu M Cd(2+), a non-specific blocker of voltage-gated Ca(2+) channels. 4. Anoxia (N(2)-equilibrated solution containing 0.5 mM dithionite) evoked exocytosis from type I cells when extracellular [K(+)] was 5 mM. This secretion was completely inhibited by removal of extracellular Ca(2+), but was not significantly affected by Cd(2+) (200 mu M), Ni(2+) (2 mM), Zn(2+) (1 mM) or nifedipine (2 mu M). Secretion was also observed when 0.5 mM dithionite was added to air-equilibrated solutions. 5. Anoxia also evoked secretion from chemoreceptive phaeochromocytoma (PC12) cells, which was wholly Ca(2+) dependent, but unaffected by Cd(2+) (200 mu M). 6. Our results suggest that hypoxia can evoke catecholamine secretion from isolated type I cells, but only in the presence of elevated extracellular [K(+)]. This may be due to the cells being relatively hyperpolarized following dissociation. In addition, we have shown that dithionite evokes catecholamine release regardless of POP levels, and this release is due mainly to an artefactual Ca(2+) influx pathway activated in the presence of dithionite.
