Effects of hypoxia and dithionite on catecholamine release from isolated type I cells of the rat carotid body

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. Hypoxia ( P O 2 8–14 mmHg) consistently failed to evoke catecholamine secretion from type I cells, when cells were perfused either at room temperature (21-24 °C) or at 35–37 °C, and regardless of whether Hepes- or HCO 3 − /CO 2 -buffered solutions were used. 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 O 2 8–14 mmHg) caused a marked enhancement of secretion which was fully blocked by 200 μM Cd 2+ , a non-specific blocker of voltage-gated Ca 2+ channels. 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 μM), Ni 2+ (2 mM), Zn 2+ (1 mM) or nifedipine (2 μM). Secretion was also observed when 0·5 mM dithionite was added to air-equilibrated solutions. Anoxia also evoked secretion from chemoreceptive phaeochromocytoma (PC12) cells, which was wholly Ca 2+ dependent, but unaffected by Cd 2+ (200 μM). 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 P O 2 levels, and this release is due mainly to an artefactual Ca 2+ influx pathway activated in the presence of dithionite.