Evidence for a common oxygen sensor for chemosensory discharge and HIF1a expression in glomus cells in rat carotid body

Abstract

Addition of a partial pressure of carbon monoxide (PCO ~ 350 Torr) to a normoxic medium (PO2 ~ 130 Torr), was used to investigate the relationship between carotid body (CB)sensory discharge and expression of hypoxia-inducible factor-1 (HIF-1) in glomus cells. Afferent electrical activity measured for in vitro perfused rat CB increased rapidly (2–3 seconds)with addition of high CO (PCO ~ 350 Torr; Po2 ~ 130 Torr) and this increase was fully reversedby white light. At submaximal light intensities, the extent of reversal was much greater formonochromatic light at 430 nm and 590 nm than for light at 450 nm, 550 nm 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 inthe presence of high CO (PCO ~ 350 Torr; Po2 ~ 130 Torr) in the dark, the levels of HIF-1, which turns 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 nm and 590 nm light was much more effective than that at 450, 550, and 610 nm in blocking the CO induced increase in HIF-1, as was observed for the CO induced increase in chemoreceptor discharge. This similarity indicates they are responding to the same oxygen sensor.