Mechanisms of acute oxygen sensing by the carotid body: Lessons from genetically modified animals

We have studied carotid body (CB) glomus cell sensitivity to changes in O2 tension in three different genetically engineered animals models using thin CB slices and monitoring the secretory response to hypoxia by amperometry. Glomus cells from partially HIF-1α deficient mice exhibited a normal sensitivity to hypoxia. Animals with complete deletion of the small membrane anchoring subunit of succinate dehydrogenase (SDHD) died during embryonic life but heterozygous SDHD +/− mice showed a normal CB response to low O2 tension. SDHD +/− mice had, however, a clear CB phenotype characterized by a decrease of K+ current amplitude, an increase of basal catecholamine release from glomus cells, and a slight organ growth. The lack of hemeoxygenase-2 (HO-2), a ubiquitous powerful antioxidant enzyme, produces a notable CB phenotype, characterized by hypertrophy and alteration in the level of CB expression of some stress-dependent genes (including down-regulation of the maxi-K+ channel α-subunit). Nevertheless, in HO-2 deficient mice the exquisite intrinsic O2 responsiveness of CB glomus cells remains unaltered. Therefore, HO-2 is not absolutely necessary for acute CB O2 sensing. Although the nature of the CB acute O2 sensor(s) is yet unknown, studies similar to those summarized here serve to test the existing hypothesis and help to distinguish between those that need to be explored further and those that definitively lack experimental support.