Hypoxia transduction by carotid body chemoreceptors in mice lacking dopamine D2 receptors

Abstract

Hypoxia-induced dopamine (DA) release from carotid body (CB) glomus cells and activation of postsynaptic D2 receptors have been proposed to play an important role in the neurotransmission process between the glomus cells and afferent nerve endings. To better resolve the role of D2 receptors, we examined afferent nerve activity, catecholamine content and release, and ventilation of genetically engineered mice lacking D2 receptors (D2−/− mice). Single-unit afferent nerve activities of D2−/− mice in vitro were significantly reduced by 45% and 25% compared with wild-type (WT) mice during superfusion with saline equilibrated with mild hypoxia (Po2 ∼50 Torr) or severe hypoxia (Po2 ∼20 Torr), respectively. Catecholamine release in D2−/− mice was enhanced by 125% in mild hypoxia and 75% in severe hypoxia compared with WT mice, and the rate of rise was increased in D2−/− mice. We conclude that CB transduction of hypoxia is still present in D2−/− mice, but the response magnitude is reduced. However, the ventilatory response to acute hypoxia is maintained, perhaps because of an enhanced processing of chemoreceptor input by brain stem respiratory nuclei.