Gene expression analyses reveal metabolic specifications in acute O-2-sensing chemoreceptor cells

Abstract

Acute O2sensing is a fundamental property of cells in the peripheral chemoreceptors,e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM),and is necessary for adaptation to hypoxia. These cells contain O2-sensitive ion channels, whichmediate membrane depolarization and transmitter release upon exposure to hypoxia. However,the mechanisms underlying the detection of changes in O2tension by cells are still poorly under-stood. Recently, we suggested that CB glomus cells have specific metabolic features that favourthe accumulation of reduced quinone and the production of mitochondrial NADH and reactiveoxygen species during hypoxia. These signals alter membrane ion channel activity. To investigatethe metabolic profile characteristic of acute O2-sensing cells, we used adult mice to comparethe transcriptomes of three cell types derived from common sympathoadrenal progenitors, butexhibiting variable responsiveness to acute hypoxia: CB and AM cells, which are O2-sensitive(glomus cells>chromaffin cells), and superior cervical ganglion neurons, which are practicallyO2-insensitive. In the O2-sensitive cells, we found a characteristic mRNA expression pattern ofprolyl hydroxylase 3/hypoxia inducible factor 2αand up-regulation of several genes, in particularthree atypical mitochondrial electron transport subunits and some ion channels. In addition, wefound that pyruvate carboxylase, an enzyme fundamental to tricarboxylic acid cycle anaplerosis, isoverexpressed in CB glomus cells. We also observed that the inhibition of succinate dehydrogenaseimpairs CB acute O2sensing. Our data suggest that responsiveness to acute hypoxia depends ona ‘signature metabolic profile’ in chemoreceptor cells.