Rat carotid body chemosensory discharge and glomus cell HIF-1α expression in vitro: regulation by a common oxygen sensor

Abstract

Addition of Pco (∼350 Torr) to a normoxic medium (Po2 of ∼130 Torr) was used to investigate the relationship between carotid body (CB) sensory discharge and expression of hypoxia-inducible factor 1α (HIF-1α) in glomus cells. Afferent electrical activity measured for in vitro -perfused rat CB increased rapidly (1–2 s) with addition of high CO (Pco of ∼350 Torr; Po2 of ∼130 Torr), and this increase was fully reversed by white light. At submaximal light intensities, the extent of reversal was much greater for monochromatic light at 430 and 590 nm than for light at 450, 550, and 610 nm. This wavelength dependence is consistent with the action spectrum of the CO compound of mitochondrial cytochrome a3. Interestingly, when isolated glomus cells cultured for 45 min in the presence of high CO (Pco of ∼350 Torr; Po2 of ∼130 Torr) in the dark, the levels of HIF-1α, which turn over slowly (many minutes), increased. This increase was not observed if the cells were illuminated with white light during the incubation. Monochromatic light at 430- and 590-nm light was much more effective than that at 450, 550, and 610 nm in blocking the CO-induced increase in HIF-1α, as was the case for chemoreceptor discharge. Although the changes in HIF-1α take minutes and those for CB neural activity occur in 1–2 s, the similar responses to CO and light suggest that the oxygen sensor is the same (mitochondrial cytochrome a3).