Impaired Acute Hypoxic Sensing in Olfactory Receptor 78 Knockout Mice

Abstract

Chang et al. (2015) reported that olfactory receptor 78 knockout (Olfr78 KO) mice exhibit impaired breathing and carotid body (CB) responses to hypoxia. However, a recent study questioned this finding (Lopez‐Barneo et al. 2018). To resolve the controversy, present study was performed on age and gender matched wild‐type (WT) and Olfr78 KO mice on Bl6 and Jax background strains (n=10 mice each genotype). Breathing was monitored in conscious mice by plethysmography and expressed as minute ventilation; VE/VO2, as well as by recording phrenic nerve activity (minute neural respiration; MNR, AU) in anesthetized mice. Hypoxia (12%O2)‐evoked increase in VE/VO2 and MNR were significantly attenuated in Olfr78 KO mice on Bl6 and Jax backgrounds, respectively as compared to WT mice (p<0.01). Hypoxia (pO2 ~35mmHg)–induced CB sensory excitation was 61 and 43% less in Olfr78‐Bl6 and Jax, respectively as compared to WT mice (p<0.01), and this effect was associated with 78% reduction in [Ca2+]i response of CB glomus cells to hypoxia (p< 0.01). In contrast, breathing and CB sensory nerve responses to 10%CO2 were comparable between Olfr78 KO (both Bl6 and Jax) and WT mice. These findings demonstrate that Olfr78 KO mice have impaired breathing, CB sensory, and glomus cell responses to acute hypoxia.Support or Funding InformationSupported by NIH‐HLBI P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.