Impaired carotid body hypoxic sensing in mice deficient in olfactory receptor 78

Abstract

Carotid bodies are the sensory organs for detecting hypoxemia (decreased arterial blood oxygen levels) and ensuing chemo reflex is a major regulator of breathing and blood pressure. Chang et al (2015) proposed that olfactory receptor 78 (Olfr78) plays a major role in hypoxic sensing by the carotid body. However, such a possibility was questioned by a subsequent study ((Torres-Torrelo et al. 2018). The discrepancy between the two reports prompted the present study to re-examine the role of Olfr78 in hypoxic sensing by the carotid body (CB). Studies were performed on age and gender matched Olfr78 knock out mice generated on BL6 and JAX backgrounds and corresponding wild type mice. Breathing was monitored by plethysmography in un-sedated and efferent phrenic nerve activity in anesthetized mice. Carotid body sensory nerve activity was determined ex vivo and [Ca2+]i responses were monitored in isolated glomus cells, the primary O2 sensing cells of the carotid body. Olfr78 null mice on both BL6 and JAX backgrounds exhibited attenuated hypoxic ventilatory response, whereas breathing responses to CO2 were unaffected. The magnitude of hyperoxia-induced depression of breathing (Dejours test), which is an indirect measure of carotid body hypoxic sensing, was markedly reduced in Olfr78 mutant mice on both background strains. Furthermore, carotid body sensory nerve and glomus cell [Ca2+]i responses to hypoxia were attenuated in BL6 and JAX Olfr78 null mice. These results suggest that Olfr78 plays an important role in hypoxic sensing by the carotid body.