Dopaminergic Properties of Cultured Rat Carotid Body Chemoreceptors Grown in Normoxic and Hypoxic Environments
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Abstract: Using dissociated carotid body (CB) cultures prepared from neonatal (postnatal days 5–7; P7) or juvenile (postnatal day 19–20; P20) rats, we compared catecholaminergic properties and mechanisms of O2 sensing in glomus cells grown in normoxic (Nox; 20% O2) and chronically hypoxic (CHox; 6% O2) environments for up to 2 weeks. In Nox cultures, basal dopamine (DA) release, determined by HPLC and normalized to the number of tyrosine hydroxylase‐positive glomus cells present, was similar for P7 and P20 cultures (∼0.3 pmol/1,000 cells/15 min) and was unaffected by culture duration (2 vs. 12 days). Acute hypoxia (5 and 10% O2) caused a dose‐dependent stimulation (6× and 3× basal, respectively) in DA release, that was inhibited by nifedipine (10 µM). DA release was also stimulated by high extracellular K+ (30 mM) and iberiotoxin (200 nM), a selective blocker of Po2‐regulated, Ca‐dependent K+ channel in glomus cells. The stimulatory effect of iberiotoxin was similar to 5% O2 in P20 cultures, but substantially less (about one‐half) in P7 cultures. In contrast, in CHox cultures, basal DA release was substantially elevated, ∼8× Nox levels, although this did not correlate with significant differences in stores. Further, whereas acute hypoxia (5% O2) and high K+ also stimulated DA release in CHox cultures (∼2× and ∼3× basal), iberiotoxin (200 nM) did not. Thus, after chronic hypoxia in vitro, there is an enhanced basal catecholamine release and an apparent down‐regulation of functional Ca‐dependent K+ channels in CB chemoreceptors. These cellular adaptations may relate to changes in CB chemosensitivity during chronic hypoxemia.
