Publication Date:
2015-11-13
Description:
Animals have evolved homeostatic responses to changes in oxygen availability that act on different timescales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long-term responses to low oxygen (hypoxia) has been established, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor gene Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that, in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765808/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Andy J -- Ortega, Fabian E -- Riegler, Johannes -- Madison, Daniel V -- Krasnow, Mark A -- K12 HL089989/HL/NHLBI NIH HHS/ -- MH065541/MH/NIMH NIH HHS/ -- NS069375/NS/NINDS NIH HHS/ -- P30 NS069375/NS/NINDS NIH HHS/ -- R01 MH065541/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Nov 12;527(7577):240-4. doi: 10.1038/nature15721.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California 94305-5307, USA. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560302" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anoxia/genetics/metabolism
;
Calcium Signaling
;
Carotid Body/cytology/drug effects/metabolism
;
Carotid Sinus/innervation
;
Female
;
HEK293 Cells
;
Humans
;
Hypercapnia/genetics/metabolism
;
Lactic Acid/*metabolism/pharmacology
;
Mice
;
Olfactory Receptor Neurons/*metabolism
;
Oxygen/blood/*metabolism
;
Receptors, Odorant/deficiency/*metabolism
;
*Respiration
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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