Co-Binding Chromophores in Oxygen Chemoreception in the Carotid Body

Abstract

The mechanism of O₂ chemoreception in the carotid body (CB) is not clear. Previously, we provided evidence (Mulligan et al., 1981; Mulligan & Lahiri, 1982; Shirahata et al., 1987) that inhibitors of mitochondrial oxidative phosphorylation specifically blocked the excitatory response to hypoxia. We further demonstrated that it is the energy production rather than O₂ consumption alone that is critical. More recently, Duchen and Biscoe (1992) showed similar responses of glomus cell [Ca²⁺]_i to hypoxia. With the discovery of O₂ sensitive K⁺ channels in glomus cells (e.g., Lopez-Barneo et al., 1988; Delpiano and Heschler, 1989), Gonzalez et al. (1992) discounted the metabolic hypothesis of O₂ chemoreception. A distinction between the two hypotheses can be made by applying appropriate ratios of CO/O₂ to the carotid body and measuring chemosensory and/or glomus cell responses. CO specifically prevents reaction of cytochrome oxidase (Keilin, 1970) with O2 and should manifest a hypoxia-like effect on the one hand, as shown by Joels and Neil (1962), and binding with hemoglobin-like pigment, would behave like O₂ and reverse the stimulatory effect of hypoxia, as proposed by Lloyd et al. (1968). We tested these predictions using the cat carotid body perfused and superfused in vitro with cell-free physiological solution and recording the chemosensory responses.