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 O(2) 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-1alpha 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 O(2) 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 alpha-subunit). Nevertheless, in HO-2 deficient mice the exquisite intrinsic O(2) responsiveness of CB glomus cells remains unaltered. Therefore, HO-2 is not absolutely necessary for acute CB O(2) sensing. Although the nature of the CB acute O(2) 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.
Ortega-Sáenz
Patricia
P
Laboratorio de Investigaciones Biomédicas, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain.
Pascual
Alberto
A
Piruat
José I
JI
López-Barneo
José
J
D000818:Animals; D030801:Animals, Genetically Modified; D002344:Carotid Body / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010100:Oxygen / Q000097:blood
D006899:Mixed Function Oxygenases; D010100:Oxygen